Variant chr22-50744827-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001097.3(ACR):c.886A>G(p.Met296Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,600,480 control chromosomes in the GnomAD database, including 374,742 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 34480 hom., cov: 22)

Exomes 𝑓: 0.68 ( 340262 hom. )

Consequence

ACR
NM_001097.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.457

Variant links:

Genes affected

ACR (HGNC:126): (acrosin) Acrosin is the major proteinase present in the acrosome of mature spermatozoa. It is a typical serine proteinase with trypsin-like specificity. It is stored in the acrosome in its precursor form, proacrosin. The active enzyme functions in the lysis of the zona pellucida, thus facilitating penetration of the sperm through the innermost glycoprotein layers of the ovum. The mRNA for proacrosin is synthesized only in the postmeiotic stages of spermatogenesis. In humans proacrosin first appears in the haploid spermatids. [provided by RefSeq, Jul 2008]

ACR 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=1.2673811E-6).

BP6

Variant 22-50744827-A-G is Benign according to our data. Variant chr22-50744827-A-G is described in ClinVar as [Benign]. Clinvar id is 402336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACR	NM_001097.3 linkuse as main transcript	c.886A>G	p.Met296Val	missense_variant	5/5	ENST00000216139.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACR	ENST00000216139.10 linkuse as main transcript	c.886A>G	p.Met296Val	missense_variant	5/5	1	NM_001097.3	P1
ACR	ENST00000527761.1 linkuse as main transcript	n.345A>G		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.680

AC:

100960

AN:

148446

Hom.:

34452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.663

Gnomad AMI

AF:

0.763

Gnomad AMR

AF:

0.689

Gnomad ASJ

AF:

0.726

Gnomad EAS

AF:

0.812

Gnomad SAS

AF:

0.804

Gnomad FIN

AF:

0.712

Gnomad MID

AF:

0.653

Gnomad NFE

AF:

0.663

Gnomad OTH

AF:

0.651

GnomAD3 exomes

AF:

0.712

AC:

136773

AN:

192086

Hom.:

48908

AF XY:

0.715

AC XY:

73632

AN XY:

102976

show subpopulations

Gnomad AFR exome

AF:

0.667

Gnomad AMR exome

AF:

0.730

Gnomad ASJ exome

AF:

0.742

Gnomad EAS exome

AF:

0.806

Gnomad SAS exome

AF:

0.807

Gnomad FIN exome

AF:

0.713

Gnomad NFE exome

AF:

0.664

Gnomad OTH exome

AF:

0.700

GnomAD4 exome

AF:

0.683

AC:

991752

AN:

1451922

Hom.:

340262

Cov.:

AF XY:

0.687

AC XY:

495550

AN XY:

721412

show subpopulations

Gnomad4 AFR exome

AF:

0.667

Gnomad4 AMR exome

AF:

0.729

Gnomad4 ASJ exome

AF:

0.740

Gnomad4 EAS exome

AF:

0.832

Gnomad4 SAS exome

AF:

0.806

Gnomad4 FIN exome

AF:

0.711

Gnomad4 NFE exome

AF:

0.664

Gnomad4 OTH exome

AF:

0.687

GnomAD4 genome

AF:

0.680

AC:

101030

AN:

148558

Hom.:

34480

Cov.:

AF XY:

0.683

AC XY:

49361

AN XY:

72304

show subpopulations

Gnomad4 AFR

AF:

0.663

Gnomad4 AMR

AF:

0.689

Gnomad4 ASJ

AF:

0.726

Gnomad4 EAS

AF:

0.812

Gnomad4 SAS

AF:

0.803

Gnomad4 FIN

AF:

0.712

Gnomad4 NFE

AF:

0.663

Gnomad4 OTH

AF:

0.646

Alfa

AF:

0.674

Hom.:

5909

Bravo

AF:

0.679

ExAC

AF:

0.682

AC:

80091

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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: 73% of total chromosomes in ExAC -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.34

DANN

Benign

0.41

DEOGEN2

Benign

0.23

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.018

MetaRNN

Benign

0.0000013

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.64

REVEL

Benign

0.16

Sift

Benign

0.11

Sift4G

Benign

0.31

Polyphen

0.020

Vest4

0.053

ClinPred

0.011

GERP RS

1.3

Varity_R

0.073

gMVP

0.23

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