Variant X-64268967-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.1685T>G(p.Leu562Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000463 in 1,209,891 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.000026 ( 0 hom. 8 hem. )

Consequence

MTMR8
NM_017677.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023612887).

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTMR8	NM_017677.4 linkuse as main transcript	c.1685T>G	p.Leu562Arg	missense_variant	14/14	ENST00000374852.4	NP_060147.2
LOC112268307	XM_047442705.1 linkuse as main transcript	c.170+21161A>C		intron_variant			XP_047298661.1
LOC112268307	XM_047442706.1 linkuse as main transcript	c.126-36599A>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.1685T>G	p.Leu562Arg	missense_variant	14/14	1	NM_017677.4	ENSP00000363985	P1	Q96EF0-1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

111960

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

34106

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000944

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

183333

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

67785

show subpopulations

Gnomad AFR exome

AF:

0.00144

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000255

AC:

AN:

1097931

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

363291

show subpopulations

Gnomad4 AFR exome

AF:

0.00106

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000250

AC:

AN:

111960

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

34106

show subpopulations

Gnomad4 AFR

AF:

0.000845

Gnomad4 AMR

AF:

0.0000944

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000176

Hom.:

Bravo

AF:

0.000257

ESP6500AA

AF:

0.00156

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

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

Nov 30, 2022

The c.1685T>G (p.L562R) 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 1685, causing the leucine (L) at amino acid position 562 to be replaced by an arginine (R). 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

0.081

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.48

M_CAP

Benign

0.045

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.33

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.51

REVEL

Uncertain

0.29

Sift

Uncertain

0.018

Sift4G

Benign

0.20

Polyphen

0.52

Vest4

0.23

MVP

0.52

MPC

0.0031

ClinPred

0.014

GERP RS

2.5

Varity_R

0.22

gMVP

0.26

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