Variant 22-41699569-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000401548.8(MEI1):c.31A>C(p.Thr11Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,459,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

MEI1
ENST00000401548.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.276

Variant links:

Genes affected

MEI1 (HGNC:28613): (meiotic double-stranded break formation protein 1) Predicted to be involved in meiosis I. Predicted to act upstream of or within gamete generation; meiotic spindle organization; and meiotic telomere clustering. Implicated in gestational trophoblastic neoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MEI1 links:

MEI1 (HGNC:):

MEI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041797817).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEI1	NM_152513.4 linkuse as main transcript	c.31A>C	p.Thr11Pro	missense_variant	1/31	ENST00000401548.8	NP_689726.3	Q5TIA1-1Q4G0I1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEI1	ENST00000401548.8 linkuse as main transcript	c.31A>C	p.Thr11Pro	missense_variant	1/31	1	NM_152513.4	ENSP00000384115.3		Q5TIA1-1
MEI1	ENST00000540833 linkuse as main transcript	c.-750A>C		5_prime_UTR_variant	1/20	5		ENSP00000444225.1		F5GZT0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000250

AC:

AN:

239792

Hom.:

AF XY:

0.0000229

AC XY:

AN XY:

131246

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000188

Gnomad OTH exome

AF:

0.000683

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1459706

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000422

Hom.:

ExAC

AF:

0.0000415

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jan 24, 2024

The c.31A>C (p.T11P) alteration is located in exon 1 (coding exon 1) of the MEI1 gene. This alteration results from a A to C substitution at nucleotide position 31, causing the threonine (T) at amino acid position 11 to be replaced by a proline (P). 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

0.050

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.9

DANN

Benign

0.44

DEOGEN2

Benign

0.056

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.25

M_CAP

Benign

0.0012

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.50

REVEL

Benign

0.019

Sift

Benign

0.29

Sift4G

Benign

0.32

Polyphen

0.0

Vest4

0.13

MutPred

0.16

Loss of phosphorylation at T11 (P = 0.0068);

MVP

0.048

MPC

0.13

ClinPred

0.035

GERP RS

-0.37

Varity_R

0.082

gMVP

0.16

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