Variant 8-97644666-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000336273.8(MTDH):c.160G>A(p.Val54Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00518 in 1,608,056 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 34 hom. )

Consequence

MTDH
ENST00000336273.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.05

Variant links:

Genes affected

MTDH (HGNC:29608): (metadherin) Enables NF-kappaB binding activity; double-stranded RNA binding activity; and transcription coactivator activity. Involved in several processes, including lipopolysaccharide-mediated signaling pathway; positive regulation of intracellular signal transduction; and regulation of transcription, DNA-templated. Located in endoplasmic reticulum; nuclear lumen; and perinuclear region of cytoplasm. Implicated in hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

MTDH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009610981).

BP6

Variant 8-97644666-G-A is Benign according to our data. Variant chr8-97644666-G-A is described in ClinVar as [Benign]. Clinvar id is 770948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTDH	NM_178812.4 linkuse as main transcript	c.160G>A	p.Val54Met	missense_variant	1/12	ENST00000336273.8	NP_848927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTDH	ENST00000336273.8 linkuse as main transcript	c.160G>A	p.Val54Met	missense_variant	1/12	1	NM_178812.4	ENSP00000338235	P1
MTDH	ENST00000519934.5 linkuse as main transcript	c.91G>A	p.Val31Met	missense_variant	1/11	5		ENSP00000428168

Frequencies

GnomAD3 genomes

AF:

0.00350

AC:

532

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00626

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00322

AC:

772

AN:

239504

Hom.:

AF XY:

0.00326

AC XY:

427

AN XY:

131002

show subpopulations

Gnomad AFR exome

AF:

0.000566

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.000922

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.00562

Gnomad OTH exome

AF:

0.00303

GnomAD4 exome

AF:

0.00535

AC:

7793

AN:

1455730

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

3827

AN XY:

724170

show subpopulations

Gnomad4 AFR exome

AF:

0.000863

Gnomad4 AMR exome

AF:

0.00182

Gnomad4 ASJ exome

AF:

0.000810

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00152

Gnomad4 FIN exome

AF:

0.00229

Gnomad4 NFE exome

AF:

0.00639

Gnomad4 OTH exome

AF:

0.00515

GnomAD4 genome

AF:

0.00349

AC:

532

AN:

152326

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

231

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00626

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00509

Hom.:

Bravo

AF:

0.00346

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.000683

AC:

ESP6500EA

AF:

0.00548

AC:

ExAC

AF:

0.00319

AC:

386

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

T;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.31

LIST_S2

Uncertain

0.88

D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.0096

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

0.87

N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.48

N;N

REVEL

Benign

0.049

Sift

Benign

0.056

T;T

Sift4G

Benign

0.085

T;T

Polyphen

0.81

P;.

Vest4

0.44

MVP

0.25

MPC

0.72

ClinPred

0.046

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.25

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