Variant 22-41699707-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_152513.4(MEI1):c.169G>C(p.Val57Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,570,484 control chromosomes in the GnomAD database, including 344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.016 ( 49 hom., cov: 34)

Exomes 𝑓: 0.013 ( 295 hom. )

Consequence

MEI1
NM_152513.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.53

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019328594).

BP6

Variant 22-41699707-G-C is Benign according to our data. Variant chr22-41699707-G-C is described in ClinVar as [Benign]. Clinvar id is 3038177.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEI1	NM_152513.4 linkuse as main transcript	c.169G>C	p.Val57Leu	missense_variant	1/31	ENST00000401548.8	NP_689726.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEI1	ENST00000401548.8 linkuse as main transcript	c.169G>C	p.Val57Leu	missense_variant	1/31	1	NM_152513.4	ENSP00000384115	P1	Q5TIA1-1
MEI1	ENST00000540833.1 linkuse as main transcript	c.-612G>C		5_prime_UTR_variant	1/20	5		ENSP00000444225

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2484

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00904

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0579

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.0254

Gnomad SAS

AF:

0.0472

Gnomad FIN

AF:

0.0209

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00819

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.0256

AC:

4351

AN:

169998

Hom.:

116

AF XY:

0.0250

AC XY:

2315

AN XY:

92762

show subpopulations

Gnomad AFR exome

AF:

0.00830

Gnomad AMR exome

AF:

0.0695

Gnomad ASJ exome

AF:

0.00440

Gnomad EAS exome

AF:

0.0236

Gnomad SAS exome

AF:

0.0468

Gnomad FIN exome

AF:

0.0205

Gnomad NFE exome

AF:

0.00782

Gnomad OTH exome

AF:

0.0222

GnomAD4 exome

AF:

0.0128

AC:

18214

AN:

1418136

Hom.:

295

Cov.:

AF XY:

0.0135

AC XY:

9474

AN XY:

701678

show subpopulations

Gnomad4 AFR exome

AF:

0.00803

Gnomad4 AMR exome

AF:

0.0686

Gnomad4 ASJ exome

AF:

0.00428

Gnomad4 EAS exome

AF:

0.0255

Gnomad4 SAS exome

AF:

0.0452

Gnomad4 FIN exome

AF:

0.0192

Gnomad4 NFE exome

AF:

0.00798

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0164

AC:

2496

AN:

152348

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1373

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00904

Gnomad4 AMR

AF:

0.0587

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.0253

Gnomad4 SAS

AF:

0.0470

Gnomad4 FIN

AF:

0.0209

Gnomad4 NFE

AF:

0.00819

Gnomad4 OTH

AF:

0.0236

Alfa

AF:

0.00816

Hom.:

Bravo

AF:

0.0191

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00594

AC:

ESP6500EA

AF:

0.00694

AC:

ExAC

AF:

0.0158

AC:

1797

Asia WGS

AF:

0.0400

AC:

138

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MEI1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.056

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.030

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

0.70

D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.92

REVEL

Benign

0.0080

Sift

Benign

0.13

Sift4G

Benign

0.087

Polyphen

0.15

Vest4

0.088

MutPred

0.18

Loss of sheet (P = 0.0181);

MPC

0.13

ClinPred

0.0070

GERP RS

3.4

Varity_R

0.090

gMVP

0.11

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