Genetic Variant ACR:p.Met296Leu (chr22-50744827-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001097.3(ACR):c.886A>T(p.Met296Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M296V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ACR
NM_001097.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.457

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07634139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACR	NM_001097.3 link	c.886A>T	p.Met296Leu	missense_variant	Exon 5 of 5	ENST00000216139.10	NP_001088.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACR	ENST00000216139.10 link	c.886A>T	p.Met296Leu	missense_variant	Exon 5 of 5	1	NM_001097.3	ENSP00000216139.5
ACR	ENST00000527761.1 link	n.345A>T		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148706

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1452282

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721634

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33090

American (AMR)

AF:

0.00

AC:

AN:

43684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25914

East Asian (EAS)

AF:

0.00

AC:

AN:

39124

South Asian (SAS)

AF:

0.00

AC:

AN:

84892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1107414

Other (OTH)

AF:

0.00

AC:

AN:

60012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

148706

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72306

African (AFR)

AF:

0.00

AC:

AN:

40168

American (AMR)

AF:

0.00

AC:

AN:

15066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

4788

South Asian (SAS)

AF:

0.00

AC:

AN:

4602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67164

Other (OTH)

AF:

0.00

AC:

AN:

2040

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.16

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.17

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.024

M_CAP

Benign

0.035

MetaRNN

Benign

0.076

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.6

PhyloP100

-0.46

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.24

REVEL

Benign

0.17

Sift

Benign

0.86

Sift4G

Benign

0.80

Polyphen

0.0

Vest4

0.11

MutPred

0.31

Loss of MoRF binding (P = 0.084);

MVP

0.75

ClinPred

0.021

GERP RS

1.3

Varity_R

0.075

gMVP

0.18

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over