chr7-76048190-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4BP6_Very_StrongBP7
The NM_005918.4(MDH2):c.30C>T(p.Ser10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 1,536,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 35)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
MDH2
NM_005918.4 synonymous
NM_005918.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.47
Genes affected
MDH2 (HGNC:6971): (malate dehydrogenase 2) Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the mitochondria and may play pivotal roles in the malate-aspartate shuttle that operates in the metabolic coordination between cytosol and mitochondria. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.13).
BP6
Variant 7-76048190-C-T is Benign according to our data. Variant chr7-76048190-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1641449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.47 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MDH2 | NM_005918.4 | c.30C>T | p.Ser10= | synonymous_variant | 1/9 | ENST00000315758.10 | |
MDH2 | NM_001282403.2 | c.30C>T | p.Ser10= | synonymous_variant | 1/8 | ||
MDH2 | NM_001282404.2 | c.-123C>T | 5_prime_UTR_variant | 1/8 | |||
MDH2 | NR_104165.2 | n.85C>T | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MDH2 | ENST00000315758.10 | c.30C>T | p.Ser10= | synonymous_variant | 1/9 | 1 | NM_005918.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000525 AC: 8AN: 152256Hom.: 0 Cov.: 35
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GnomAD3 exomes AF: 0.0000427 AC: 6AN: 140576Hom.: 0 AF XY: 0.0000659 AC XY: 5AN XY: 75898
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GnomAD4 exome AF: 0.0000304 AC: 42AN: 1383748Hom.: 0 Cov.: 36 AF XY: 0.0000351 AC XY: 24AN XY: 683120
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GnomAD4 genome AF: 0.0000525 AC: 8AN: 152256Hom.: 0 Cov.: 35 AF XY: 0.0000672 AC XY: 5AN XY: 74386
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | MDH2: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 30, 2023 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 06, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at