chrX-64271062-C-T

Position:

• chrX-64271062-C-T

Variant summary

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

The ENST00000374852.4(MTMR8):​c.1493G>A​(p.Gly498Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: MTMR8 ENST00000374852.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.61

Genes affected

MTMR8 (HGNC:16825): (myotubularin related protein 8) This gene encodes a member of the myotubularin-related family and is part of the MTMR6 subgroup. Family members are dual-specificity phosphatases and the encoded protein contains a phosphoinositide-binding domain (PID) and a SET-interacting domain (SID). Defects in other family members have been found in myotubular myopathic diseases. [provided by RefSeq, Mar 2010]

LOC112268307 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR8	NM_017677.4	c.1493G>A	p.Gly498Glu	missense_variant	13/14	ENST00000374852.4	NP_060147.2
LOC112268307	XM_047442705.1	c.170+23256C>T		intron_variant			XP_047298661.1
LOC112268307	XM_047442706.1	c.126-34504C>T		intron_variant			XP_047298662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR8	ENST00000374852.4	c.1493G>A	p.Gly498Glu	missense_variant	13/14	1	NM_017677.4	ENSP00000363985.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Richard Lifton Laboratory, Yale University School of Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	0.84	D;D
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.45
Sift	Benign	0.075	T
Sift4G	Uncertain	0.032	D
Polyphen		0.78	P
Vest4		0.68
MutPred		0.43		Loss of MoRF binding (P = 0.1112);
MVP		0.44
MPC		0.0035
ClinPred		0.96	D
GERP RS		2.9
Varity_R		0.55
gMVP		0.45

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

Other links and lift over

dbSNP: rs386352332; hg19: chrX-63490942;