Variant 11-125678274-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001612.6(ACRV1):c.76C>A(p.Leu26Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ACRV1
NM_001612.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0510

Variant links:

Genes affected

ACRV1 (HGNC:127): (acrosomal vesicle protein 1) This gene encodes a testis-specific, differentiation antigen, acrosomal vesicle protein 1, that arises within the acrosomal vesicle during spermatogenesis, and is associated with the acrosomal membranes and matrix of mature sperm. The acrosomal vesicle protein 1 may be involved in sperm-zona binding or penetration. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2010]

ACRV1 links:

CHEK1 (HGNC:):

CHEK1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023633033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACRV1	NM_001612.6 linkuse as main transcript	c.76C>A	p.Leu26Ile	missense_variant	2/4	ENST00000533904.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACRV1	ENST00000533904.6 linkuse as main transcript	c.76C>A	p.Leu26Ile	missense_variant	2/4	1	NM_001612.6	A2	P26436-1
ACRV1	ENST00000315608.7 linkuse as main transcript	c.76C>A	p.Leu26Ile	missense_variant	2/4	1		P2	P26436-2
ACRV1	ENST00000530048.5 linkuse as main transcript	c.76C>A	p.Leu26Ile	missense_variant	2/5	3		A2	P26436-3
ACRV1	ENST00000527795.1 linkuse as main transcript	c.76C>A	p.Leu26Ile	missense_variant	2/5	2		A2	P26436-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000799

AC:

AN:

250308

Hom.:

AF XY:

0.0000813

AC XY:

AN XY:

135302

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461684

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000882

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.000140

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.76C>A (p.L26I) alteration is located in exon 2 (coding exon 2) of the ACRV1 gene. This alteration results from a C to A substitution at nucleotide position 76, causing the leucine (L) at amino acid position 26 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.20

DANN

Benign

0.83

DEOGEN2

Benign

0.060

T;.;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.62

T;T;T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.024

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

L;L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.59

N;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.33

T;T;T;T

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.20

B;B;P;B

Vest4

0.10

MutPred

0.13

Gain of glycosylation at S27 (P = 0.1526);Gain of glycosylation at S27 (P = 0.1526);Gain of glycosylation at S27 (P = 0.1526);Gain of glycosylation at S27 (P = 0.1526);

MVP

0.13

MPC

0.31

ClinPred

0.043

GERP RS

-0.86

Varity_R

0.058

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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