7-76048190-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005918.4(MDH2):āc.30C>Gā(p.Ser10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_005918.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MDH2 | NM_005918.4 | c.30C>G | p.Ser10Arg | missense_variant | 1/9 | ENST00000315758.10 | NP_005909.2 | |
MDH2 | NM_001282403.2 | c.30C>G | p.Ser10Arg | missense_variant | 1/8 | NP_001269332.1 | ||
MDH2 | NM_001282404.2 | c.-123C>G | 5_prime_UTR_variant | 1/8 | NP_001269333.1 | |||
MDH2 | NR_104165.2 | n.85C>G | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 35
GnomAD3 exomes AF: 0.00000711 AC: 1AN: 140576Hom.: 0 AF XY: 0.0000132 AC XY: 1AN XY: 75898
GnomAD4 exome AF: 7.23e-7 AC: 1AN: 1383748Hom.: 0 Cov.: 36 AF XY: 0.00000146 AC XY: 1AN XY: 683120
GnomAD4 genome Cov.: 35
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 27, 2022 | The p.S10R variant (also known as c.30C>G), located in coding exon 1 of the MDH2 gene, results from a C to G substitution at nucleotide position 30. The serine at codon 10 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 10, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with MDH2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 10 of the MDH2 protein (p.Ser10Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at