rs2305799

Positions:

chr19-11576536-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.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. 13/20 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

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=0.0025962591).

BP6

Variant 19-11576536-C-T is Benign according to our data. Variant chr19-11576536-C-T is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
ACP5	NM_001611.5 linkuse as main transcript	c.442G>A	p.Val148Met	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.442G>A	p.Val148Met	missense_variant	4/5		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

GnomAD3 exomes

AF:

0.105

AC:

26367

AN:

250338

Hom.:

1583

AF XY:

0.109

AC XY:

14748

AN XY:

135396

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 SAS exome

AF:

0.0946

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

Gnomad4 AFR exome

AF:

0.0387

Gnomad4 AMR exome

AF:

0.0690

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.0823

Gnomad4 SAS exome

AF:

0.0975

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.0968

AC:

14719

AN:

152080

Hom.:

853

Cov.:

AF XY:

0.0965

AC XY:

7171

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0391

Gnomad4 AMR

AF:

0.0829

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.0841

Gnomad4 SAS

AF:

0.0899

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.120

Hom.:

2427

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

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 -
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 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. -

not provided

Benign:2

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

Spondyloenchondrodysplasia with immune dysregulation

Benign:2

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

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

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

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

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

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