rs5771002

Variant names:

• chr22-50744827-A-G
• rs5771002
• NM_001097.3:c.886A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-50744827-A-G
• chr22-50744827-A-C
• chr22-50744827-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M296I) has been classified as Uncertain significance.

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.457
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001097.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACR	NM_001097.3	MANE Select	c.886A>G	p.Met296Val	missense	Exon 5 of 5	NP_001088.2	P10323

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACR	ENST00000216139.10	TSL:1 MANE Select	c.886A>G	p.Met296Val	missense	Exon 5 of 5	ENSP00000216139.5	P10323
	ACR	ENST00000527761.1	TSL:5	n.345A>G		non_coding_transcript_exon	Exon 2 of 2

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

GnomAD2 exomes AF: 0.712 AC: 136773 AN: 192086 AF XY: 0.715

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 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

African (AFR) AF: 0.667 AC: 22066 AN: 33086

American (AMR) AF: 0.729 AC: 31852 AN: 43672

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 19179 AN: 25910

East Asian (EAS) AF: 0.832 AC: 32549 AN: 39124

South Asian (SAS) AF: 0.806 AC: 68382 AN: 84878

European-Finnish (FIN) AF: 0.711 AC: 37246 AN: 52368

Middle Eastern (MID) AF: 0.690 AC: 3974 AN: 5756

European-Non Finnish (NFE) AF: 0.664 AC: 735309 AN: 1107134

Other (OTH) AF: 0.687 AC: 41195 AN: 59994

GnomAD4 genome AF: 0.680 AC: 101030 AN: 148558 Hom.: 34480 Cov.: 22 AF XY: 0.683 AC XY: 49361 AN XY: 72304

African (AFR) AF: 0.663 AC: 26659 AN: 40200

American (AMR) AF: 0.689 AC: 10371 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2501 AN: 3444

East Asian (EAS) AF: 0.812 AC: 3869 AN: 4766

South Asian (SAS) AF: 0.803 AC: 3682 AN: 4586

European-Finnish (FIN) AF: 0.712 AC: 7257 AN: 10194

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.663 AC: 44488 AN: 67070

Other (OTH) AF: 0.646 AC: 1330 AN: 2058

Alfa AF: 0.674 Hom.: 5909

Bravo AF: 0.679

ExAC AF: 0.682 AC: 80091

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.46
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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