Variant 8-97644588-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000336273.8(MTDH):c.82G>A(p.Gly28Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,608,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MTDH
ENST00000336273.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.67

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34973204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTDH	NM_178812.4 linkuse as main transcript	c.82G>A	p.Gly28Ser	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.82G>A	p.Gly28Ser	missense_variant	1/12	1	NM_178812.4	ENSP00000338235	P1
MTDH	ENST00000519934.5 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	1/11	5		ENSP00000428168

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000125

AC:

AN:

239380

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

131210

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000278

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1456092

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

724486

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000162

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000331

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

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

Jul 19, 2022

The c.82G>A (p.G28S) alteration is located in exon 1 (coding exon 1) of the MTDH gene. This alteration results from a G to A substitution at nucleotide position 82, causing the glycine (G) at amino acid position 28 to be replaced by a serine (S). 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

0.21

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.0033

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.89

D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.8

D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0080

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.032

B;.

Vest4

0.52

MutPred

0.55

Loss of loop (P = 0.0374);.;

MVP

0.55

MPC

0.42

ClinPred

0.96

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.64

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