Variant X-64268803-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000374852.4(MTMR8):c.1849G>C(p.Gly617Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,209,652 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000031 ( 0 hom. 16 hem. )

Consequence

MTMR8
ENST00000374852.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.333

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03625968).

BP6

Variant X-64268803-C-G is Benign according to our data. Variant chrX-64268803-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2660750.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR8	NM_017677.4 linkuse as main transcript	c.1849G>C	p.Gly617Arg	missense_variant	14/14	ENST00000374852.4	NP_060147.2	Q96EF0-1
LOC112268307	XM_047442705.1 linkuse as main transcript	c.170+20997C>G		intron_variant			XP_047298661.1
LOC112268307	XM_047442706.1 linkuse as main transcript	c.126-36763C>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.1849G>C	p.Gly617Arg	missense_variant	14/14	1	NM_017677.4	ENSP00000363985.3		Q96EF0-1

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111367

Hom.:

Cov.:

AF XY:

0.0000596

AC XY:

AN XY:

33549

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000763

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000655

AC:

AN:

183335

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

67777

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000577

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000310

AC:

AN:

1098233

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

363587

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:

0.000610

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111419

Hom.:

Cov.:

AF XY:

0.0000595

AC XY:

AN XY:

33611

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000766

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

MTMR8: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.19

CADD

Benign

2.3

DANN

Benign

0.64

DEOGEN2

Benign

0.080

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.53

M_CAP

Benign

0.037

MetaRNN

Benign

0.036

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.090

REVEL

Uncertain

0.36

Sift

Uncertain

0.017

Sift4G

Benign

0.10

Polyphen

0.53

Vest4

0.068

MVP

0.52

MPC

0.0039

ClinPred

0.044

GERP RS

0.59

Varity_R

0.11

gMVP

0.16

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