chr8-97644813-C-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_178812.4(MTDH):c.307C>G(p.Leu103Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,574,454 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0076 ( 10 hom., cov: 32)
Exomes 𝑓: 0.0032 ( 28 hom. )
Consequence
MTDH
NM_178812.4 missense
NM_178812.4 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 0.205
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0023199022).
BP6
?
Variant 8-97644813-C-G is Benign according to our data. Variant chr8-97644813-C-G is described in ClinVar as [Benign]. Clinvar id is 2658702.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00319 (4541/1422098) while in subpopulation MID AF= 0.0247 (138/5588). AF 95% confidence interval is 0.0213. There are 28 homozygotes in gnomad4_exome. There are 2442 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 10 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTDH | NM_178812.4 | c.307C>G | p.Leu103Val | missense_variant | 1/12 | ENST00000336273.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTDH | ENST00000336273.8 | c.307C>G | p.Leu103Val | missense_variant | 1/12 | 1 | NM_178812.4 | P1 | |
MTDH | ENST00000519934.5 | c.238C>G | p.Leu80Val | missense_variant | 1/11 | 5 | |||
MTDH | ENST00000522313.1 | c.22C>G | p.Leu8Val | missense_variant | 1/5 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00755 AC: 1149AN: 152240Hom.: 10 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00489 AC: 965AN: 197530Hom.: 8 AF XY: 0.00503 AC XY: 560AN XY: 111256
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GnomAD4 exome AF: 0.00319 AC: 4541AN: 1422098Hom.: 28 Cov.: 31 AF XY: 0.00345 AC XY: 2442AN XY: 707856
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GnomAD4 genome ? AF: 0.00756 AC: 1152AN: 152356Hom.: 10 Cov.: 32 AF XY: 0.00769 AC XY: 573AN XY: 74510
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ESP6500AA
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ExAC
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580
Asia WGS
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AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | MTDH: BS1, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at