Genetic Variant MEI1:p.Thr11Pro (chr22-41699569-A-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_152513.4(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. 15/22 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
NM_152513.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.276

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hydatidiform mole, recurrent, 3
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
complete hydatidiform mole
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MEI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

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

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000151 (22/1459706) while in subpopulation MID AF = 0.000893 (5/5596). AF 95% confidence interval is 0.000352. There are 0 homozygotes in GnomAdExome4. There are 14 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152513.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEI1	NM_152513.4	MANE Select	c.31A>C	p.Thr11Pro	missense	Exon 1 of 31	NP_689726.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEI1	ENST00000401548.8	TSL:1 MANE Select	c.31A>C	p.Thr11Pro	missense	Exon 1 of 31	ENSP00000384115.3	Q5TIA1-1
MEI1	ENST00000890163.1		c.31A>C	p.Thr11Pro	missense	Exon 1 of 30	ENSP00000560222.1
MEI1	ENST00000540833.1	TSL:5	c.-750A>C		5_prime_UTR	Exon 1 of 20	ENSP00000444225.1	F5GZT0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000250

AC:

AN:

239792

AF XY:

0.0000229

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 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

African (AFR)

AF:

0.00

AC:

AN:

33396

American (AMR)

AF:

0.00

AC:

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.000128

AC:

AN:

86158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52826

Middle Eastern (MID)

AF:

0.000893

AC:

AN:

5596

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111160

Other (OTH)

AF:

0.0000664

AC:

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000270

Hom.:

ExAC

AF:

0.0000415

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.9

(source)

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

PhyloP100

-0.28

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

PromoterAI

0.097

Neutral

(source)

Varity_R

0.082

gMVP

0.16

Mutation Taster

=296/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over