NM_001190.4:c.1010G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001190.4(BCAT2):​c.1010G>C​(p.Gly337Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G337S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

BCAT2
NM_001190.4 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.40
Variant links:
Genes affected
BCAT2 (HGNC:977): (branched chain amino acid transaminase 2) This gene encodes a branched chain aminotransferase found in mitochondria. The encoded protein forms a dimer that catalyzes the first step in the production of the branched chain amino acids leucine, isoleucine, and valine. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

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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 rank MANE Protein UniProt
BCAT2NM_001190.4 linkc.1010G>C p.Gly337Ala missense_variant Exon 9 of 11 ENST00000316273.11 NP_001181.2 O15382-1
BCAT2NM_001284325.2 linkc.890G>C p.Gly297Ala missense_variant Exon 10 of 12 NP_001271254.1 O15382B3KSI3
BCAT2NM_001164773.2 linkc.734G>C p.Gly245Ala missense_variant Exon 7 of 9 NP_001158245.1 O15382-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BCAT2ENST00000316273.11 linkc.1010G>C p.Gly337Ala missense_variant Exon 9 of 11 1 NM_001190.4 ENSP00000322991.5 O15382-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Apr 13, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with BCAT2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 337 of the BCAT2 protein (p.Gly337Ala). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Uncertain
0.065
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
.;T;T;T;T;T;T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;.;D;D;D;D;D
M_CAP
Benign
0.039
D
MetaRNN
Uncertain
0.66
D;D;D;D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
.;.;L;.;.;.;.
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-5.5
D;D;D;.;.;.;.
REVEL
Benign
0.25
Sift
Uncertain
0.0020
D;D;D;.;.;.;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D
Polyphen
1.0
D;D;D;.;D;.;.
Vest4
0.84
MutPred
0.60
.;.;Loss of glycosylation at S338 (P = 0.1028);.;.;.;Loss of glycosylation at S338 (P = 0.1028);
MVP
0.66
MPC
1.3
ClinPred
1.0
D
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.93
gMVP
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-49299890; API