Variant X-64268859-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000374852.4(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
ENST00000374852.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.525

Variant links:

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]

MTMR8 links:

LOC112268307 (HGNC:):

LOC112268307 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.1793T>C	p.Met598Thr	missense_variant	14/14	ENST00000374852.4	NP_060147.2	Q96EF0-1
LOC112268307	XM_047442705.1 linkuse as main transcript	c.170+21053A>G		intron_variant			XP_047298661.1
LOC112268307	XM_047442706.1 linkuse as main transcript	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 linkuse as main transcript	c.1793T>C	p.Met598Thr	missense_variant	14/14	1	NM_017677.4	ENSP00000363985.3		Q96EF0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1098211

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363565

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.052

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.36

M_CAP

Benign

0.085

MetaRNN

Benign

0.065

MetaSVM

Uncertain

-0.11

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.48

PROVEAN

Benign

0.080

REVEL

Benign

0.28

Sift

Uncertain

0.0030

Sift4G

Benign

0.094

Polyphen

0.0

Vest4

0.066

MutPred

0.29

Gain of phosphorylation at M598 (P = 0.0598);

MVP

0.63

MPC

0.0029

ClinPred

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over