X-150727244-A-T

Position:

• chrX-150727244-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001306144.3(MTMR1):​c.382A>T​(p.Met128Leu) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: MTMR1 NM_001306144.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64

Genes affected

MTMR1 (HGNC:7449): (myotubularin related protein 1) This gene encodes a member of the myotubularin related family of proteins. Members of this family contain the consensus sequence for the active site of protein tyrosine phosphatases. Alternatively spliced variants have been described but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19445214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR1	NM_001306144.3	c.382A>T	p.Met128Leu	missense_variant	5/16	ENST00000445323.7	NP_001293073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR1	ENST00000445323.7	c.382A>T	p.Met128Leu	missense_variant	5/16	1	NM_001306144.3	ENSP00000414178.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 24

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

Apr 06, 2022

The c.358A>T (p.M120L) alteration is located in exon 4 (coding exon 4) of the MTMR1 gene. This alteration results from a A to T substitution at nucleotide position 358, causing the methionine (M) at amino acid position 120 to be replaced by a leucine (L). 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	0.080
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	8.9
DANN	Benign	0.67
DEOGEN2	Uncertain	0.51	D;D;D;D;D;.;.;T;D;D
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.68	T;T;.;T;T;T;T;T;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.49	.;.;.;.;N;.;.;.;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.92	N;N;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.68	T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.65	T;T;T;T;T;T;T;T;T;T
Polyphen		0.0, 0.0010	.;.;.;.;B;.;B;B;.;.
Vest4		0.24, 0.24, 0.23
MutPred		0.52		.;.;.;.;.;.;.;Loss of catalytic residue at G129 (P = 0.1498);.;.;
MVP		0.75
ClinPred		0.063	T
GERP RS		-0.21
Varity_R		0.10
gMVP		0.65

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: chrX-149895716;