Variant X-64331569-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000374852.4(MTMR8):c.1340G>A(p.Arg447Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,207,699 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.000024 ( 0 hom. 5 hem. )

Consequence

MTMR8
ENST00000374852.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

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:

MTMR8 (HGNC:):

MTMR8 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR8	NM_017677.4 linkuse as main transcript	c.1340G>A	p.Arg447Gln	missense_variant	11/14	ENST00000374852.4	NP_060147.2	Q96EF0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MTMR8	ENST00000374852.4 linkuse as main transcript	c.1340G>A	p.Arg447Gln	missense_variant	11/14	1	NM_017677.4	ENSP00000363985.3	Q96EF0-1
MTMR8	ENST00000462447.5 linkuse as main transcript	n.500G>A		non_coding_transcript_exon_variant	4/4	3
MTMR8	ENST00000478487.5 linkuse as main transcript	n.539G>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.000233

AC:

AN:

111475

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

AN XY:

33695

show subpopulations

Gnomad AFR

AF:

0.000782

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000609

AC:

AN:

180621

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

65593

show subpopulations

Gnomad AFR exome

AF:

0.000766

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000237

AC:

AN:

1096170

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

361938

show subpopulations

Gnomad4 AFR exome

AF:

0.000721

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000996

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000476

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000233

AC:

AN:

111529

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

AN XY:

33759

show subpopulations

Gnomad4 AFR

AF:

0.000780

Gnomad4 AMR

AF:

0.000191

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000178

Hom.:

Bravo

AF:

0.000181

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

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 08, 2021

The c.1340G>A (p.R447Q) alteration is located in exon 11 (coding exon 11) of the MTMR8 gene. This alteration results from a G to A substitution at nucleotide position 1340, causing the arginine (R) at amino acid position 447 to be replaced by a glutamine (Q). 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

Uncertain

0.48

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.39

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.89

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.42

MetaRNN

Uncertain

0.53

MetaSVM

Pathogenic

0.99

MutationAssessor

Pathogenic

3.8

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.7

REVEL

Pathogenic

0.80

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.49

MVP

0.70

MPC

0.010

ClinPred

0.71

GERP RS

2.7

Varity_R

0.52

gMVP

0.68

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