Variant 22-50744984-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001097.3(ACR):c.1043C>T(p.Pro348Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 12)

Exomes 𝑓: 0.000080 ( 1 hom. )

Consequence

ACR
NM_001097.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.812

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012367487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACR	NM_001097.3 linkuse as main transcript	c.1043C>T	p.Pro348Leu	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.1043C>T	p.Pro348Leu	missense_variant	5/5	1	NM_001097.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000143

AC:

AN:

104802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000784

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00123

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000466

AC:

AN:

83776

Hom.:

AF XY:

0.000393

AC XY:

AN XY:

43292

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00208

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:

0.000751

GnomAD4 exome

AF:

0.0000803

AC:

AN:

884726

Hom.:

Cov.:

AF XY:

0.0000611

AC XY:

AN XY:

442230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00228

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:

0.00

Gnomad4 OTH exome

AF:

0.000148

GnomAD4 genome

AF:

0.000143

AC:

AN:

104882

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

AN XY:

49002

show subpopulations

Gnomad4 AFR

AF:

0.0000781

Gnomad4 AMR

AF:

0.00123

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000169

Hom.:

ExAC

AF:

0.0000598

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

Jul 07, 2022

The c.1043C>T (p.P348L) alteration is located in exon 5 (coding exon 5) of the ACR gene. This alteration results from a C to T substitution at nucleotide position 1043, causing the proline (P) at amino acid position 348 to be replaced by a leucine (L). 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

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

Cadd

Benign

2.3

Dann

Benign

0.85

DEOGEN2

Uncertain

0.44

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.047

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.83

REVEL

Uncertain

0.30

Sift

Benign

0.67

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.16

MutPred

0.41

Loss of glycosylation at P348 (P = 0.0018);

MVP

0.90

ClinPred

0.018

GERP RS

2.2

Varity_R

0.034

gMVP

0.14

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