19-11576380-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.598G>A(p.Val200Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,610,798 control chromosomes in the GnomAD database, including 10,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 734 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9374 hom. )

Consequence

ACP5
NM_001611.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.03

Publications

26 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=0.00640592).

BP6

Variant 19-11576380-C-T is Benign according to our data. Variant chr19-11576380-C-T is described in ClinVar as Benign. ClinVar VariationId is 257479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP5	NM_001611.5 link	c.598G>A	p.Val200Met	missense_variant	Exon 4 of 5	ENST00000648477.1	NP_001602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP5	ENST00000648477.1 link	c.598G>A	p.Val200Met	missense_variant	Exon 4 of 5		NM_001611.5	ENSP00000496973.1

Frequencies

GnomAD3 genomes

AF:

0.0877

AC:

13346

AN:

152102

Hom.:

733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0281

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.0757

Gnomad ASJ

AF:

0.0963

Gnomad EAS

AF:

0.0846

Gnomad SAS

AF:

0.0882

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.104

GnomAD2 exomes

AF:

0.0971

AC:

24160

AN:

248768

AF XY:

0.101

show subpopulations

Gnomad AFR exome

AF:

0.0269

Gnomad AMR exome

AF:

0.0613

Gnomad ASJ exome

AF:

0.0885

Gnomad EAS exome

AF:

0.0839

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.111

AC:

161535

AN:

1458576

Hom.:

9374

Cov.:

AF XY:

0.111

AC XY:

80313

AN XY:

725064

show subpopulations

African (AFR)

AF:

0.0254

AC:

850

AN:

33410

American (AMR)

AF:

0.0647

AC:

2892

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.0898

AC:

2345

AN:

26108

East Asian (EAS)

AF:

0.0823

AC:

3258

AN:

39604

South Asian (SAS)

AF:

0.0954

AC:

8219

AN:

86170

European-Finnish (FIN)

AF:

0.134

AC:

7042

AN:

52570

Middle Eastern (MID)

AF:

0.145

AC:

813

AN:

5614

European-Non Finnish (NFE)

AF:

0.117

AC:

129603

AN:

1110222

Other (OTH)

AF:

0.108

AC:

6513

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

9045

18090

27135

36180

45225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4654

9308

13962

18616

23270

<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:

0.0877

AC:

13345

AN:

152222

Hom.:

734

Cov.:

AF XY:

0.0871

AC XY:

6479

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0280

AC:

1162

AN:

41566

American (AMR)

AF:

0.0755

AC:

1154

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0963

AC:

334

AN:

3468

East Asian (EAS)

AF:

0.0846

AC:

438

AN:

5176

South Asian (SAS)

AF:

0.0876

AC:

422

AN:

4816

European-Finnish (FIN)

AF:

0.137

AC:

1448

AN:

10606

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7984

AN:

67996

Other (OTH)

AF:

0.105

AC:

222

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

611

1223

1834

2446

3057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.109

Hom.:

4120

Bravo

AF:

0.0812

TwinsUK

AF:

0.114

AC:

421

ALSPAC

AF:

0.109

AC:

421

ESP6500AA

AF:

0.0286

AC:

126

ESP6500EA

AF:

0.110

AC:

942

ExAC

AF:

0.0952

AC:

11554

Asia WGS

AF:

0.0860

AC:

298

AN:

3478

EpiCase

AF:

0.119

EpiControl

AF:

0.121

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. 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

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

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

0.28

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;D;D;D;D

Eigen

Benign

0.0070

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.0

.;.;.;.;D

MetaRNN

Benign

0.0064

T;T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.8

M;M;M;M;M

PhyloP100

1.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

0.0

.;N;N;.;N

REVEL

Benign

0.0

Sift

Pathogenic

0.0

.;D;D;.;D

Sift4G

Pathogenic

0.0

.;D;D;D;D

Vest4

0.0

ClinPred

0.039

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.37

gMVP

0.62

Mutation Taster

=98/2

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