chr8-17302209-A-G

Position:

chr8-17302209-A-G

Variant summary

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

The NM_004686.5(MTMR7):c.1565T>C(p.Met522Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00277 in 1,614,098 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 12 hom. )

Consequence

MTMR7
NM_004686.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.11

Variant links:

Genes affected

MTMR7 (HGNC:7454): (myotubularin related protein 7) This gene encodes a member of the myotubularin family of tyrosine/dual-specificity phosphatases. The encoded protein is characterized by four distinct domains that are conserved among all members of the myotubularin family: the glucosyltransferase, Rab-like GTPase activator and myotubularins domain, the Rac-induced recruitment domain, the protein tyrosine phosphatases and dual-specificity phosphatases domain and the suppressor of variegation 3-9, enhancer-of-zeste, and trithorax interaction domain. This protein dephosphorylates the target substrates phosphatidylinositol 3-phosphate and inositol 1,3-bisphosphate. A pseudogene of this gene is found on chromosome 5. [provided by RefSeq, Mar 2009]

MTMR7 links:

VPS37A (HGNC:24928): (VPS37A subunit of ESCRT-I) This gene belongs to the VPS37 family, and encodes a component of the ESCRT-I (endosomal sorting complex required for transport I) protein complex, required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies. Expression of this gene is downregulated in hepatocellular carcinoma, and mutations in this gene are associated with autosomal recessive spastic paraplegia-53. A related pseudogene has been identified on chromosome 5. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

VPS37A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011514902).

BP6

Variant 8-17302209-A-G is Benign according to our data. Variant chr8-17302209-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3042663.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR7	NM_004686.5 linkuse as main transcript	c.1565T>C	p.Met522Thr	missense_variant	13/14	ENST00000180173.10	NP_004677.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR7	ENST00000180173.10 linkuse as main transcript	c.1565T>C	p.Met522Thr	missense_variant	13/14	1	NM_004686.5	ENSP00000180173	P1	Q9Y216-1
MTMR7	ENST00000521857.5 linkuse as main transcript	c.1565T>C	p.Met522Thr	missense_variant	13/13	5		ENSP00000429733		Q9Y216-2
MTMR7	ENST00000519590.5 linkuse as main transcript	n.577T>C		non_coding_transcript_exon_variant	4/4	4
VPS37A	ENST00000519515.1 linkuse as main transcript	n.53-5A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00230

AC:

350

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00461

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00359

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00192

AC:

482

AN:

251174

Hom.:

AF XY:

0.00181

AC XY:

246

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00351

Gnomad NFE exome

AF:

0.00285

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.00282

AC:

4115

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

2025

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00132

Gnomad4 FIN exome

AF:

0.00346

Gnomad4 NFE exome

AF:

0.00323

Gnomad4 OTH exome

AF:

0.00237

GnomAD4 genome

AF:

0.00230

AC:

350

AN:

152294

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00461

Gnomad4 NFE

AF:

0.00359

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00282

Hom.:

Bravo

AF:

0.00184

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00197

AC:

239

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00300

EpiControl

AF:

0.00237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MTMR7-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 03, 2022

This variant is classified as likely 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

0.19

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.27

T;.

Eigen

Benign

-0.034

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.11

Sift

Benign

0.12

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.080

B;B

Vest4

0.73

MVP

0.71

MPC

0.020

ClinPred

0.015

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.44

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