chr8-97725681-A-G

Variant names:

• chr8-97725681-A-G
• rs2449512
• NM_178812.4:c.*1011A>G

Variant summary

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

The NM_178812.4(MTDH):​c.*1011A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0968 in 152,620 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: 4.03
• Publications: 8 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=-0.54).
• 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 rank	MANE	Protein	UniProt
MTDH	NM_178812.4	c.*1011A>G		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.*1011A>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_178812.4	ENSP00000338235.3

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14713 AN: 152070 Hom.: 1045 Cov.: 33

Gnomad AFR AF: 0.0728

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: 0.0732

Gnomad NFE AF: 0.0674

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: 14721 AN: 152188 Hom.: 1051 Cov.: 33 AF XY: 0.103 AC XY: 7668 AN XY: 74406

African (AFR) AF: 0.0726 AC: 3016 AN: 41522

American (AMR) AF: 0.193 AC: 2952 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3472

East Asian (EAS) AF: 0.297 AC: 1541 AN: 5186

South Asian (SAS) AF: 0.194 AC: 939 AN: 4830

European-Finnish (FIN) AF: 0.110 AC: 1160 AN: 10584

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.0674 AC: 4581 AN: 68008

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

Alfa AF: 0.0780 Hom.: 982

Bravo AF: 0.102

Asia WGS AF: 0.218 AC: 756 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.82
PhyloP100		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2449512; hg19: chr8-98737909;