Genetic Variant MEI1:p.Thr11Ala (chr22-41699569-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_152513.4(MEI1):c.31A>G(p.Thr11Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000246 in 1,611,902 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T11P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00024 ( 3 hom. )

Consequence

MEI1
NM_152513.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036006868).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000302 (46/152196) while in subpopulation AMR AF = 0.00222 (34/15282). AF 95% confidence interval is 0.00164. There are 0 homozygotes in GnomAd4. There are 27 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

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>G	p.Thr11Ala	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>G	p.Thr11Ala	missense	Exon 1 of 31	ENSP00000384115.3	Q5TIA1-1
MEI1	ENST00000890163.1		c.31A>G	p.Thr11Ala	missense	Exon 1 of 30	ENSP00000560222.1
MEI1	ENST00000540833.1	TSL:5	c.-750A>G		5_prime_UTR	Exon 1 of 20	ENSP00000444225.1	F5GZT0

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

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

GnomAD2 exomes

AF:

0.00131

AC:

315

AN:

239792

AF XY:

0.000968

show subpopulations

Gnomad AFR exome

AF:

0.0000686

Gnomad AMR exome

AF:

0.00904

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000169

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000342

GnomAD4 exome

AF:

0.000240

AC:

351

AN:

1459706

Hom.:

Cov.:

AF XY:

0.000198

AC XY:

144

AN XY:

726164

show subpopulations

African (AFR)

AF:

0.0000599

AC:

AN:

33396

American (AMR)

AF:

0.00751

AC:

335

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39642

South Asian (SAS)

AF:

0.00

AC:

AN:

86158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52826

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5596

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111160

Other (OTH)

AF:

0.000149

AC:

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.000302

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41516

American (AMR)

AF:

0.00222

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000270

Hom.:

Bravo

AF:

0.000676

ExAC

AF:

0.000904

AC:

109

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.2

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.035

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.28

M_CAP

Benign

0.0019

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

PhyloP100

-0.28

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.15

REVEL

Benign

0.0050

Sift

Benign

0.76

Sift4G

Benign

0.80

Polyphen

0.0

Vest4

0.091

MVP

0.014

MPC

0.097

ClinPred

0.014

GERP RS

-0.37

PromoterAI

0.30

Neutral

(source)

Varity_R

0.026

gMVP

0.17

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over