22-41705550-T-G

Position:

• chr22-41705550-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152513.4(MEI1):​c.345T>G​(p.Ile115Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MEI1 NM_152513.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.823

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2705729).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEI1	NM_152513.4	c.345T>G	p.Ile115Met	missense_variant	3/31	ENST00000401548.8	NP_689726.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEI1	ENST00000401548.8	c.345T>G	p.Ile115Met	missense_variant	3/31	1	NM_152513.4	ENSP00000384115	P1
MEI1	ENST00000540833.1	c.-436T>G		5_prime_UTR_variant	3/20	5		ENSP00000444225

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2022

The c.345T>G (p.I115M) alteration is located in exon 3 (coding exon 3) of the MEI1 gene. This alteration results from a T to G substitution at nucleotide position 345, causing the isoleucine (I) at amino acid position 115 to be replaced by a methionine (M). 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	0.088
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.11
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.040	D
Polyphen		0.99	D
Vest4		0.37
MutPred		0.29		Gain of catalytic residue at I115 (P = 0.0545);
MVP		0.34
MPC		0.46
ClinPred		0.79	D
GERP RS		3.5
Varity_R		0.096
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-42101554;