chr8-17300096-A-C

Position:

chr8-17300096-A-C

Variant summary

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

The NM_004686.5(MTMR7):c.1749T>G(p.Ser583Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 1,614,040 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 13 hom. )

Consequence

MTMR7
NM_004686.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0940

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=0.0057281256).

BP6

Variant 8-17300096-A-C is Benign according to our data. Variant chr8-17300096-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3044627.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR7	NM_004686.5 linkuse as main transcript	c.1749T>G	p.Ser583Arg	missense_variant	14/14	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.1749T>G	p.Ser583Arg	missense_variant	14/14	1	NM_004686.5	ENSP00000180173	P1	Q9Y216-1
VPS37A	ENST00000520997.1 linkuse as main transcript	n.441A>C		non_coding_transcript_exon_variant	3/3	3
VPS37A	ENST00000521162.5 linkuse as main transcript	n.783A>C		non_coding_transcript_exon_variant	3/3	2
VPS37A	ENST00000519515.1 linkuse as main transcript	n.52+1938A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00230

AC:

349

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00410

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00218

AC:

548

AN:

251082

Hom.:

AF XY:

0.00228

AC XY:

310

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00199

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00392

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00391

AC:

5715

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

2839

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00202

Gnomad4 FIN exome

AF:

0.000674

Gnomad4 NFE exome

AF:

0.00471

Gnomad4 OTH exome

AF:

0.00336

GnomAD4 genome

AF:

0.00229

AC:

349

AN:

152170

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00410

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00358

Hom.:

Bravo

AF:

0.00225

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00224

AC:

272

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00420

EpiControl

AF:

0.00326

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

Nov 29, 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

0.24

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Benign

7.5

DANN

Benign

0.96

DEOGEN2

Benign

0.16

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.77

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.85

M_CAP

Benign

0.038

MetaRNN

Benign

0.0057

MetaSVM

Benign

-0.54

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.94

D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.41

Sift

Benign

0.28

Sift4G

Benign

0.55

Polyphen

0.20

Vest4

0.25

MutPred

0.21

Loss of glycosylation at S583 (P = 0.0105);

MVP

0.71

MPC

0.027

ClinPred

0.0055

GERP RS

-2.6

Varity_R

0.11

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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