Variant 8-97644813-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_178812.4(MTDH):c.307C>G(p.Leu103Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,574,454 control chromosomes in the GnomAD database, including 38 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 28 hom. )

Consequence

MTDH
NM_178812.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.205

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023199022).

BP6

Variant 8-97644813-C-G is Benign according to our data. Variant chr8-97644813-C-G is described in ClinVar as [Benign]. Clinvar id is 2658702.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00319 (4541/1422098) while in subpopulation MID AF= 0.0247 (138/5588). AF 95% confidence interval is 0.0213. There are 28 homozygotes in gnomad4_exome. There are 2442 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTDH	NM_178812.4 linkuse as main transcript	c.307C>G	p.Leu103Val	missense_variant	1/12	ENST00000336273.8	NP_848927.2	Q86UE4A0A024R9D2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MTDH	ENST00000336273.8 linkuse as main transcript	c.307C>G	p.Leu103Val	missense_variant	1/12	1	NM_178812.4	ENSP00000338235.3	Q86UE4
MTDH	ENST00000519934.5 linkuse as main transcript	c.238C>G	p.Leu80Val	missense_variant	1/11	5		ENSP00000428168.1	E5RJU9
MTDH	ENST00000522313.1 linkuse as main transcript	c.19C>G	p.Leu7Val	missense_variant	1/5	4		ENSP00000428703.1	H0YB56

Frequencies

GnomAD3 genomes

AF:

0.00755

AC:

1149

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0151

Gnomad AMI

AF:

0.0286

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00951

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.00489

AC:

965

AN:

197530

Hom.:

AF XY:

0.00503

AC XY:

560

AN XY:

111256

show subpopulations

Gnomad AFR exome

AF:

0.0137

Gnomad AMR exome

AF:

0.00608

Gnomad ASJ exome

AF:

0.0286

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00879

Gnomad FIN exome

AF:

0.000146

Gnomad NFE exome

AF:

0.00207

Gnomad OTH exome

AF:

0.00737

GnomAD4 exome

AF:

0.00319

AC:

4541

AN:

1422098

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

2442

AN XY:

707856

show subpopulations

Gnomad4 AFR exome

AF:

0.0146

Gnomad4 AMR exome

AF:

0.00657

Gnomad4 ASJ exome

AF:

0.0329

Gnomad4 EAS exome

AF:

0.0000558

Gnomad4 SAS exome

AF:

0.00946

Gnomad4 FIN exome

AF:

0.000117

Gnomad4 NFE exome

AF:

0.00156

Gnomad4 OTH exome

AF:

0.00757

GnomAD4 genome

AF:

0.00756

AC:

1152

AN:

152356

Hom.:

Cov.:

AF XY:

0.00769

AC XY:

573

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0151

Gnomad4 AMR

AF:

0.0125

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00952

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00565

Hom.:

Bravo

AF:

0.00853

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00943

AC:

ESP6500EA

AF:

0.00185

AC:

ExAC

AF:

0.00490

AC:

580

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

MTDH: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.036

T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.62

T;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

N;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.090

N;N

REVEL

Benign

0.047

Sift

Benign

0.68

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.0

B;.

Vest4

0.091

MVP

0.10

MPC

0.32

ClinPred

0.00096

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.30

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