2-206755156-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001039845.3(MDH1B):c.763G>A(p.Val255Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000836 in 1,614,202 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000084 ( 0 hom. )
Consequence
MDH1B
NM_001039845.3 missense
NM_001039845.3 missense
Scores
14
5
Clinical Significance
Conservation
PhyloP100: 4.46
Genes affected
MDH1B (HGNC:17836): (malate dehydrogenase 1B) Predicted to enable L-malate dehydrogenase activity. Predicted to be involved in NADH metabolic process; dicarboxylic acid metabolic process; and tricarboxylic acid cycle. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MDH1B | NM_001039845.3 | c.763G>A | p.Val255Met | missense_variant | 5/12 | ENST00000374412.8 | NP_001034934.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MDH1B | ENST00000374412.8 | c.763G>A | p.Val255Met | missense_variant | 5/12 | 1 | NM_001039845.3 | ENSP00000363533 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251404Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135872
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GnomAD4 exome AF: 0.0000841 AC: 123AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.0000921 AC XY: 67AN XY: 727248
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74486
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2023 | The c.763G>A (p.V255M) alteration is located in exon 5 (coding exon 5) of the MDH1B gene. This alteration results from a G to A substitution at nucleotide position 763, causing the valine (V) at amino acid position 255 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
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