rs1311

Variant names:

• chr8-97726133-T-C
• rs1311
• NM_178812.4:c.*1463T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178812.4(MTDH):​c.*1463T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0968 in 152,626 control chromosomes in the GnomAD database, including 1,054 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 (1051 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: 5.53
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTDH	NM_178812.4	c.*1463T>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000336273.8	NP_848927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTDH	ENST00000336273.8	c.*1463T>C		3_prime_UTR_variant	Exon 12 of 12	1	NM_178812.4	ENSP00000338235.3

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14709 AN: 152076 Hom.: 1045 Cov.: 33

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0675

Gnomad OTH AF: 0.0920

GnomAD4 exome AF: 0.125 AC: 54 AN: 432 Hom.: 3 Cov.: 0 AF XY: 0.135 AC XY: 35 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.127 AC: 54 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0967 AC: 14717 AN: 152194 Hom.: 1051 Cov.: 33 AF XY: 0.103 AC XY: 7666 AN XY: 74390

African (AFR) AF: 0.0724 AC: 3006 AN: 41548

American (AMR) AF: 0.194 AC: 2956 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1540 AN: 5162

South Asian (SAS) AF: 0.194 AC: 938 AN: 4828

European-Finnish (FIN) AF: 0.110 AC: 1161 AN: 10596

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0674 AC: 4584 AN: 68000

Other (OTH) AF: 0.0929 AC: 196 AN: 2110

Alfa AF: 0.0779 Hom.: 980

Bravo AF: 0.101

Asia WGS AF: 0.218 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.89
PhyloP100		5.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1311; hg19: chr8-98738361;