22-50744827-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.457

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	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	c.886A>G	p.Met296Val	missense_variant	5/5	1	NM_001097.3	P1
ACR	ENST00000527761.1	n.345A>G		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.680 AC: 100960 AN: 148446 Hom.: 34452 Cov.: 22

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

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.: 47 AF XY: 0.687 AC XY: 495550 AN XY: 721412

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.: 22 AF XY: 0.683 AC XY: 49361 AN XY: 72304

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:1

Revision: criteria provided, single submitter

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	0.34
Dann	Benign	0.41
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.018	N
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.16
Sift	Benign	0.11	T
Sift4G	Benign	0.31	T
Polyphen		0.020	B
Vest4		0.053
ClinPred		0.011	T
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

Other links and lift over

dbSNP: rs5771002; hg19: chr22-51183255; COSMIC: COSV53360317; COSMIC: COSV53360317;