chrX-64268859-A-G

Position:

• chrX-64268859-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017677.4(MTMR8):​c.1793T>C​(p.Met598Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,098,211 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: MTMR8 NM_017677.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.525

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06462559).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR8	NM_017677.4	c.1793T>C	p.Met598Thr	missense_variant	14/14	ENST00000374852.4	NP_060147.2
LOC112268307	XM_047442705.1	c.170+21053A>G		intron_variant			XP_047298661.1
LOC112268307	XM_047442706.1	c.126-36707A>G		intron_variant			XP_047298662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR8	ENST00000374852.4	c.1793T>C	p.Met598Thr	missense_variant	14/14	1	NM_017677.4	ENSP00000363985.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098211 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363565

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000237

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

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

Dec 05, 2022

The c.1793T>C (p.M598T) alteration is located in exon 14 (coding exon 14) of the MTMR8 gene. This alteration results from a T to C substitution at nucleotide position 1793, causing the methionine (M) at amino acid position 598 to be replaced by a threonine (T). 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	0.11
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.052	T
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.065	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.094	T
Polyphen		0.0	B
Vest4		0.066
MutPred		0.29		Gain of phosphorylation at M598 (P = 0.0598);
MVP		0.63
MPC		0.0029
ClinPred		0.18	T
GERP RS		2.7
Varity_R		0.41
gMVP		0.29

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-63488739;