Variant chr22-41699645-T-A 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.107T>A(p.Leu36Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000363 in 1,597,872 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: 𝑓 0.00012 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

MEI1
ENST00000401548.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.745

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=0.04398778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEI1	NM_152513.4 linkuse as main transcript	c.107T>A	p.Leu36Gln	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.107T>A	p.Leu36Gln	missense_variant	1/31	1	NM_152513.4	ENSP00000384115.3		Q5TIA1-1
MEI1	ENST00000540833 linkuse as main transcript	c.-674T>A		5_prime_UTR_variant	1/20	5		ENSP00000444225.1		F5GZT0

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.000129

AC:

AN:

210082

Hom.:

AF XY:

0.0000953

AC XY:

AN XY:

115482

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000861

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:

0.00

GnomAD4 exome

AF:

0.0000277

AC:

AN:

1445646

Hom.:

Cov.:

AF XY:

0.0000209

AC XY:

AN XY:

718054

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000894

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:

0.0000168

GnomAD4 genome

AF:

0.000118

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00118

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:

0.0000712

Hom.:

Bravo

AF:

0.000170

ExAC

AF:

0.0000421

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 13, 2022

The c.107T>A (p.L36Q) alteration is located in exon 1 (coding exon 1) of the MEI1 gene. This alteration results from a T to A substitution at nucleotide position 107, causing the leucine (L) at amino acid position 36 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.15

Eigen

Benign

0.089

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.63

M_CAP

Benign

0.019

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.89

D;D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.9

REVEL

Benign

0.13

Sift

Benign

0.25

Sift4G

Uncertain

0.010

Polyphen

0.0050

Vest4

0.36

MutPred

0.27

Gain of solvent accessibility (P = 0.0137);

MVP

0.24

MPC

0.11

ClinPred

0.080

GERP RS

4.6

Varity_R

0.25

gMVP

0.24

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