22-50739360-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_001097.3(ACR):​c.167G>A​(p.Trp56*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

ACR
NM_001097.3 stop_gained

Scores

5
1
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.87
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 22-50739360-G-A is Pathogenic according to our data. Variant chr22-50739360-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2577998.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACRNM_001097.3 linkc.167G>A p.Trp56* stop_gained Exon 2 of 5 ENST00000216139.10 NP_001088.2 P10323

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACRENST00000216139.10 linkc.167G>A p.Trp56* stop_gained Exon 2 of 5 1 NM_001097.3 ENSP00000216139.5 P10323
ACRENST00000533930.1 linkn.207G>A non_coding_transcript_exon_variant Exon 2 of 3 1
ACRENST00000529621.1 linkc.167G>A p.Trp56* stop_gained Exon 2 of 4 5 ENSP00000435120.1 E9PLV5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Spermatogenic failure 87 Pathogenic:1
Aug 31, 2023
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.61
D
BayesDel_noAF
Pathogenic
0.63
CADD
Pathogenic
45
DANN
Uncertain
1.0
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.98
D
Vest4
0.84
GERP RS
4.8

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-51177788; API