chr19-11576380-C-T

Position:

chr19-11576380-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:

ACP5 (HGNC:):

ACP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
ACP5	NM_001611.5 linkuse as main transcript	c.598G>A	p.Val200Met	missense_variant	4/5	ENST00000648477.1	NP_001602.1	P13686A0A024R7F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACP5	ENST00000648477.1 linkuse as main transcript	c.598G>A	p.Val200Met	missense_variant	4/5		NM_001611.5	ENSP00000496973.1		P13686

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

GnomAD3 exomes

AF:

0.0971

AC:

24160

AN:

248768

Hom.:

1350

AF XY:

0.101

AC XY:

13554

AN XY:

134784

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 SAS exome

AF:

0.0926

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

Gnomad4 AFR exome

AF:

0.0254

Gnomad4 AMR exome

AF:

0.0647

Gnomad4 ASJ exome

AF:

0.0898

Gnomad4 EAS exome

AF:

0.0823

Gnomad4 SAS exome

AF:

0.0954

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.0877

AC:

13345

AN:

152222

Hom.:

734

Cov.:

AF XY:

0.0871

AC XY:

6479

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0280

Gnomad4 AMR

AF:

0.0755

Gnomad4 ASJ

AF:

0.0963

Gnomad4 EAS

AF:

0.0846

Gnomad4 SAS

AF:

0.0876

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.117

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.112

Hom.:

2355

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

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Spondyloenchondrodysplasia with immune dysregulation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

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

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

Uncertain

0.92

.;.;.;.;D

MetaRNN

Benign

0.0064

T;T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.8

M;M;M;M;M

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.44

.;N;N;.;N

REVEL

Uncertain

0.34

Sift

Uncertain

0.029

.;D;D;.;D

Sift4G

Uncertain

0.013

.;D;D;D;D

Polyphen

0.98

D;D;D;D;D

Vest4

0.10, 0.10, 0.099

MPC

0.86

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over