rs2438211

Positions:

• chr8-97725521-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178812.4(MTDH):​c.*851C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 152,528 control chromosomes in the GnomAD database, including 1,049 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.097 (1046 hom., cov: 33)
  • Exomes 𝑓: 0.13 (3 hom.)
• Consequence: MTDH NM_178812.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTDH	NM_178812.4	c.*851C>T		3_prime_UTR_variant	12/12	ENST00000336273.8	NP_848927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTDH	ENST00000336273.8	c.*851C>T		3_prime_UTR_variant	12/12	1	NM_178812.4	ENSP00000338235.3

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14696 AN: 151980 Hom.: 1040 Cov.: 33

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0920

GnomAD4 exome AF: 0.126 AC: 54 AN: 430 Hom.: 3 Cov.: 0 AF XY: 0.135 AC XY: 35 AN XY: 260

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0967 AC: 14704 AN: 152098 Hom.: 1046 Cov.: 33 AF XY: 0.103 AC XY: 7662 AN XY: 74336

Gnomad4 AFR AF: 0.0725

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.0893

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0674

Gnomad4 OTH AF: 0.0929

Alfa AF: 0.0804 Hom.: 703

Bravo AF: 0.101

Asia WGS AF: 0.218 AC: 753 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs2438211; hg19: chr8-98737749;