Variant 11-125678174-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001612.6(ACRV1):c.176C>G(p.Ser59Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ACRV1
NM_001612.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19459593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACRV1	NM_001612.6 linkuse as main transcript	c.176C>G	p.Ser59Cys	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.176C>G	p.Ser59Cys	missense_variant	2/4	1	NM_001612.6	A2	P26436-1
ACRV1	ENST00000315608.7 linkuse as main transcript	c.176C>G	p.Ser59Cys	missense_variant	2/4	1		P2	P26436-2
ACRV1	ENST00000527795.1 linkuse as main transcript	c.121+55C>G		intron_variant		2		A2	P26436-4
ACRV1	ENST00000530048.5 linkuse as main transcript	c.121+55C>G		intron_variant		3		A2	P26436-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251218

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

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

Jan 31, 2024

The c.176C>G (p.S59C) alteration is located in exon 2 (coding exon 2) of the ACRV1 gene. This alteration results from a C to G substitution at nucleotide position 176, causing the serine (S) at amino acid position 59 to be replaced by a cysteine (C). 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

0.20

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.074

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.046

Sift

Uncertain

0.023

D;D

Sift4G

Uncertain

0.038

D;D

Polyphen

0.91

P;P

Vest4

0.24

MVP

0.21

MPC

0.65

ClinPred

0.68

GERP RS

2.5

Varity_R

0.14

gMVP

0.63

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