chr19-11576317-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_001611.5(ACP5):c.661G>A(p.Val221Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 1,611,542 control chromosomes in the GnomAD database, including 612 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V221V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.035 ( 313 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 299 hom. )

Consequence

ACP5
NM_001611.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.26

Publications

4 publications found

Variant links:

Genes affected

ACP5 (HGNC:124): (acid phosphatase 5, tartrate resistant) This gene encodes an iron containing glycoprotein which catalyzes the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is the most basic of the acid phosphatases and is the only form not inhibited by L(+)-tartrate. [provided by RefSeq, Aug 2008]

ACP5 links:

ZNF627 (HGNC:30570): (zinc finger protein 627) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF627 links:

LOC124904638 (HGNC:):

LOC124904638 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

PM1

In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 7 uncertain in NM_001611.5

BP4

Computational evidence support a benign effect (MetaRNN=0.002044946).

BP6

Variant 19-11576317-C-T is Benign according to our data. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in CliVar as Benign. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP5	NM_001611.5 link	c.661G>A	p.Val221Ile	missense_variant	Exon 4 of 5	ENST00000648477.1	NP_001602.1	P13686A0A024R7F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP5	ENST00000648477.1 link	c.661G>A	p.Val221Ile	missense_variant	Exon 4 of 5		NM_001611.5	ENSP00000496973.1		P13686

Frequencies

GnomAD3 genomes

AF:

0.0354

AC:

5384

AN:

152100

Hom.:

312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00976

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0220

GnomAD2 exomes

AF:

0.00931

AC:

2313

AN:

248382

AF XY:

0.00688

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.00484

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00343

AC:

5012

AN:

1459324

Hom.:

299

Cov.:

AF XY:

0.00289

AC XY:

2096

AN XY:

725980

show subpopulations

African (AFR)

AF:

0.127

AC:

4260

AN:

33460

American (AMR)

AF:

0.00575

AC:

257

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.000162

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51430

Middle Eastern (MID)

AF:

0.00327

AC:

AN:

5512

European-Non Finnish (NFE)

AF:

0.0000405

AC:

AN:

1111870

Other (OTH)

AF:

0.00691

AC:

417

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

255

510

766

1021

1276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0354

AC:

5389

AN:

152218

Hom.:

313

Cov.:

AF XY:

0.0349

AC XY:

2596

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.125

AC:

5172

AN:

41508

American (AMR)

AF:

0.00975

AC:

149

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.000828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68026

Other (OTH)

AF:

0.0218

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

219

439

658

878

1097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0130

Hom.:

225

Bravo

AF:

0.0407

ESP6500AA

AF:

0.128

AC:

566

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0119

AC:

1443

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Spondyloenchondrodysplasia with immune dysregulation

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.27

T;T;T;T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.88

.;.;.;.;D

MetaRNN

Benign

0.0020

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;L;L;L;L

PhyloP100

2.3

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.44

.;N;N;.;N

REVEL

Benign

0.20

Sift

Benign

0.21

.;T;T;.;T

Sift4G

Benign

0.33

.;T;T;T;T

Polyphen

0.078

B;B;B;B;B

Vest4

0.095, 0.094

MPC

0.36

ClinPred

0.0037

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.47

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over