Variant 2-74581794-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001321739.2(M1AP):c.649G>A(p.Val217Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

M1AP
NM_001321739.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.373

Variant links:

Genes affected

M1AP (HGNC:25183): (meiosis 1 associated protein) This gene encodes a protein that is likely to function in progression of meiosis. A similar protein in mouse plays a role in gametogenesis in both sexes. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

M1AP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08359203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
M1AP	NM_001321739.2 linkuse as main transcript	c.649G>A	p.Val217Ile	missense_variant	5/11	ENST00000421985.2	NP_001308668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
M1AP	ENST00000421985.2 linkuse as main transcript	c.649G>A	p.Val217Ile	missense_variant	5/11	2	NM_001321739.2	ENSP00000414882	P4	Q8TC57-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251404

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

277

AN:

1461676

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

133

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000242

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.0000718

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.649G>A (p.V217I) alteration is located in exon 5 (coding exon 4) of the M1AP gene. This alteration results from a G to A substitution at nucleotide position 649, causing the valine (V) at amino acid position 217 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

M1AP: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.30

DANN

Benign

0.96

DEOGEN2

Benign

0.013

T;.;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.58

T;.;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.084

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.89

L;L;L

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.24

N;N;N

REVEL

Benign

0.037

Sift

Benign

0.40

T;T;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.16

B;.;.

Vest4

0.12

MVP

0.030

MPC

0.12

ClinPred

0.037

GERP RS

2.6

Varity_R

0.026

gMVP

0.090

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