8-97679242-A-G

Position:

• chr8-97679242-A-G

Variant summary

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

The NM_178812.4(MTDH):​c.484-7426A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 152,230 control chromosomes in the GnomAD database, including 929 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 0.093 (929 hom., cov: 31)
• Consequence: MTDH NM_178812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTDH	NM_178812.4	c.484-7426A>G		intron_variant		ENST00000336273.8	NP_848927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTDH	ENST00000336273.8	c.484-7426A>G		intron_variant		1	NM_178812.4	ENSP00000338235.3
MTDH	ENST00000519934.5	c.415-7426A>G		intron_variant		5		ENSP00000428168.1
MTDH	ENST00000522313.1	c.196-7426A>G		intron_variant		4		ENSP00000428703.1

Frequencies

GnomAD3 genomes AF: 0.0935 AC: 14216 AN: 152112 Hom.: 923 Cov.: 31

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.0881

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0672

Gnomad OTH AF: 0.0903

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0935 AC: 14228 AN: 152230 Hom.: 929 Cov.: 31 AF XY: 0.0991 AC XY: 7373 AN XY: 74422

Gnomad4 AFR AF: 0.0716

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.0881

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0671

Gnomad4 OTH AF: 0.0917

Alfa AF: 0.0410 Hom.: 43

Bravo AF: 0.0987

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.87

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: rs2438224; hg19: chr8-98691470;