chr19-11576536-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001611.5(ACP5):c.442G>A(p.Val148Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,754 control chromosomes in the GnomAD database, including 11,369 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 853 hom., cov: 31)

Exomes 𝑓: 0.12 ( 10516 hom. )

Consequence

ACP5
NM_001611.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.35

Publications

24 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025962591).

BP6

Variant 19-11576536-C-T is Benign according to our data. Variant chr19-11576536-C-T is described in ClinVar as Benign. ClinVar VariationId is 257478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) 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.442G>A	p.Val148Met	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.442G>A	p.Val148Met	missense_variant	Exon 4 of 5		NM_001611.5	ENSP00000496973.1		P13686

Frequencies

GnomAD3 genomes

AF:

0.0969

AC:

14718

AN:

151962

Hom.:

852

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0392

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.0830

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.0841

Gnomad SAS

AF:

0.0905

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.117

GnomAD2 exomes

AF:

0.105

AC:

26367

AN:

250338

AF XY:

0.109

show subpopulations

Gnomad AFR exome

AF:

0.0393

Gnomad AMR exome

AF:

0.0649

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.0844

Gnomad FIN exome

AF:

0.150

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.118

AC:

172154

AN:

1461674

Hom.:

10516

Cov.:

AF XY:

0.118

AC XY:

85632

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.0387

AC:

1297

AN:

33478

American (AMR)

AF:

0.0690

AC:

3088

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

3238

AN:

26136

East Asian (EAS)

AF:

0.0823

AC:

3267

AN:

39692

South Asian (SAS)

AF:

0.0975

AC:

8412

AN:

86252

European-Finnish (FIN)

AF:

0.150

AC:

8025

AN:

53412

Middle Eastern (MID)

AF:

0.169

AC:

973

AN:

5768

European-Non Finnish (NFE)

AF:

0.123

AC:

136777

AN:

1111822

Other (OTH)

AF:

0.117

AC:

7077

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

9000

18000

27001

36001

45001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4884

9768

14652

19536

24420

<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:

0.0968

AC:

14719

AN:

152080

Hom.:

853

Cov.:

AF XY:

0.0965

AC XY:

7171

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0391

AC:

1624

AN:

41526

American (AMR)

AF:

0.0829

AC:

1265

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

431

AN:

3470

East Asian (EAS)

AF:

0.0841

AC:

434

AN:

5158

South Asian (SAS)

AF:

0.0899

AC:

433

AN:

4816

European-Finnish (FIN)

AF:

0.156

AC:

1649

AN:

10588

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.124

AC:

8439

AN:

67942

Other (OTH)

AF:

0.118

AC:

249

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

670

1340

2009

2679

3349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.114

Hom.:

4486

Bravo

AF:

0.0901

TwinsUK

AF:

0.117

AC:

433

ALSPAC

AF:

0.115

AC:

444

ESP6500AA

AF:

0.0399

AC:

176

ESP6500EA

AF:

0.119

AC:

1020

ExAC

AF:

0.103

AC:

12546

Asia WGS

AF:

0.0880

AC:

305

AN:

3478

EpiCase

AF:

0.127

EpiControl

AF:

0.130

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spondyloenchondrodysplasia with immune dysregulation

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

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

0.17

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

T;T;T;T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.70

.;.;.;.;T

MetaRNN

Benign

0.0026

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

L;L;L;L;L

PhyloP100

1.4

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.69

.;N;N;.;N

REVEL

Benign

0.095

Sift

Benign

0.11

.;T;T;.;T

Sift4G

Benign

0.12

.;T;T;T;T

Polyphen

0.56

P;P;P;P;P

Vest4

0.039, 0.037, 0.036

MPC

0.47

ClinPred

0.014

GERP RS

4.1

Varity_R

0.19

gMVP

0.78

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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