2-206749050-C-G
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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):āc.1186G>Cā(p.Glu396Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,170 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Consequence
MDH1B
NM_001039845.3 missense
NM_001039845.3 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 5.75
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.1186G>C | p.Glu396Gln | missense_variant | 7/12 | ENST00000374412.8 | NP_001034934.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MDH1B | ENST00000374412.8 | c.1186G>C | p.Glu396Gln | missense_variant | 7/12 | 1 | NM_001039845.3 | ENSP00000363533 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 33
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GnomAD4 exome Cov.: 31
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74344
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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 | Jan 09, 2024 | The c.1186G>C (p.E396Q) alteration is located in exon 7 (coding exon 7) of the MDH1B gene. This alteration results from a G to C substitution at nucleotide position 1186, causing the glutamic acid (E) at amino acid position 396 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
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;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;D;T
Polyphen
P;.;P
Vest4
MutPred
Gain of sheet (P = 0.1208);.;Gain of sheet (P = 0.1208);
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