Variant X-64268645-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_017677.4(MTMR8):c.2007C>A(p.Asn669Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00659 in 1,209,676 control chromosomes in the GnomAD database, including 46 homozygotes. There are 2,605 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0066 ( 3 hom., 275 hem., cov: 23)

Exomes 𝑓: 0.0066 ( 43 hom. 2330 hem. )

Consequence

MTMR8
NM_017677.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.154

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031017065).

BP6

Variant X-64268645-G-T is Benign according to our data. Variant chrX-64268645-G-T is described in ClinVar as [Benign]. Clinvar id is 3038272.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTMR8	NM_017677.4 linkuse as main transcript	c.2007C>A	p.Asn669Lys	missense_variant	14/14	ENST00000374852.4	NP_060147.2
LOC112268307	XM_047442705.1 linkuse as main transcript	c.170+20839G>T		intron_variant			XP_047298661.1
LOC112268307	XM_047442706.1 linkuse as main transcript	c.126-36921G>T		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.2007C>A	p.Asn669Lys	missense_variant	14/14	1	NM_017677.4	ENSP00000363985	P1	Q96EF0-1

Frequencies

GnomAD3 genomes

AF:

0.00665

AC:

741

AN:

111410

Hom.:

Cov.:

AF XY:

0.00818

AC XY:

275

AN XY:

33602

show subpopulations

Gnomad AFR

AF:

0.000751

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.0335

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000765

Gnomad FIN

AF:

0.0402

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00637

Gnomad OTH

AF:

0.00532

GnomAD3 exomes

AF:

0.00832

AC:

1526

AN:

183318

Hom.:

AF XY:

0.00757

AC XY:

513

AN XY:

67756

show subpopulations

Gnomad AFR exome

AF:

0.000608

Gnomad AMR exome

AF:

0.00193

Gnomad ASJ exome

AF:

0.0247

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000944

Gnomad FIN exome

AF:

0.0440

Gnomad NFE exome

AF:

0.00630

Gnomad OTH exome

AF:

0.00950

GnomAD4 exome

AF:

0.00658

AC:

7227

AN:

1098213

Hom.:

Cov.:

AF XY:

0.00641

AC XY:

2330

AN XY:

363567

show subpopulations

Gnomad4 AFR exome

AF:

0.000606

Gnomad4 AMR exome

AF:

0.00222

Gnomad4 ASJ exome

AF:

0.0255

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000960

Gnomad4 FIN exome

AF:

0.0416

Gnomad4 NFE exome

AF:

0.00537

Gnomad4 OTH exome

AF:

0.00731

GnomAD4 genome

AF:

0.00665

AC:

741

AN:

111463

Hom.:

Cov.:

AF XY:

0.00817

AC XY:

275

AN XY:

33665

show subpopulations

Gnomad4 AFR

AF:

0.000749

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.0335

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000767

Gnomad4 FIN

AF:

0.0402

Gnomad4 NFE

AF:

0.00637

Gnomad4 OTH

AF:

0.00526

Alfa

AF:

0.00726

Hom.:

342

Bravo

AF:

0.00447

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00386

AC:

ExAC

AF:

0.00745

AC:

904

EpiCase

AF:

0.00796

EpiControl

AF:

0.00635

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MTMR8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.5

DANN

Benign

0.95

DEOGEN2

Benign

0.055

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.49

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.59

REVEL

Benign

0.21

Sift

Uncertain

0.011

Sift4G

Uncertain

0.025

Polyphen

0.0

Vest4

0.017

MutPred

0.35

Gain of ubiquitination at N669 (P = 0.0177);

MVP

0.57

MPC

0.0029

ClinPred

0.013

GERP RS

-0.97

Varity_R

0.14

gMVP

0.14

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