Variant X-64268818-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017677.4(MTMR8):c.1834T>G(p.Cys612Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,209,499 control chromosomes in the GnomAD database, including 1 homozygotes. There are 363 hemizygotes 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: 𝑓 0.00052 ( 0 hom., 18 hem., cov: 23)

Exomes 𝑓: 0.0011 ( 1 hom. 345 hem. )

Consequence

MTMR8
NM_017677.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.537

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03225091).

BS2

High Hemizygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTMR8	NM_017677.4 linkuse as main transcript	c.1834T>G	p.Cys612Gly	missense_variant	14/14	ENST00000374852.4	NP_060147.2
LOC112268307	XM_047442705.1 linkuse as main transcript	c.170+21012A>C		intron_variant			XP_047298661.1
LOC112268307	XM_047442706.1 linkuse as main transcript	c.126-36748A>C		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.1834T>G	p.Cys612Gly	missense_variant	14/14	1	NM_017677.4	ENSP00000363985	P1	Q96EF0-1

Frequencies

GnomAD3 genomes

AF:

0.000521

AC:

AN:

111265

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

33483

show subpopulations

Gnomad AFR

AF:

0.000262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000382

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000167

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000830

Gnomad OTH

AF:

0.000664

GnomAD3 exomes

AF:

0.000513

AC:

AN:

183376

Hom.:

AF XY:

0.000560

AC XY:

AN XY:

67810

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000500

Gnomad NFE exome

AF:

0.000867

Gnomad OTH exome

AF:

0.000883

GnomAD4 exome

AF:

0.00109

AC:

1202

AN:

1098234

Hom.:

Cov.:

AF XY:

0.000949

AC XY:

345

AN XY:

363588

show subpopulations

Gnomad4 AFR exome

AF:

0.0000757

Gnomad4 AMR exome

AF:

0.000227

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000554

Gnomad4 FIN exome

AF:

0.000592

Gnomad4 NFE exome

AF:

0.00135

Gnomad4 OTH exome

AF:

0.000564

GnomAD4 genome

AF:

0.000521

AC:

AN:

111265

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

33483

show subpopulations

Gnomad4 AFR

AF:

0.000262

Gnomad4 AMR

AF:

0.000382

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000167

Gnomad4 NFE

AF:

0.000830

Gnomad4 OTH

AF:

0.000664

Alfa

AF:

0.000959

Hom.:

Bravo

AF:

0.000419

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.000743

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000771

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 01, 2022

The c.1834T>G (p.C612G) alteration is located in exon 14 (coding exon 14) of the MTMR8 gene. This alteration results from a T to G substitution at nucleotide position 1834, causing the cysteine (C) at amino acid position 612 to be replaced by a glycine (G). 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

0.066

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.16

CADD

Benign

2.7

DANN

Benign

0.13

DEOGEN2

Benign

0.098

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.34

M_CAP

Benign

0.0088

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.35

Sift

Benign

0.14

Sift4G

Benign

0.31

Polyphen

0.032

Vest4

0.13

MVP

0.56

MPC

0.0031

ClinPred

0.0086

GERP RS

1.5

Varity_R

0.097

gMVP

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over