rs11548193

chr19-48799813-G-Achr19-48799813-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001190.4(BCAT2):c.557C>T(p.Thr186Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T186R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: BCAT2 NM_001190.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19984695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCAT2	NM_001190.4	c.557C>T	p.Thr186Met	missense_variant	6/11	ENST00000316273.11
BCAT2	NM_001284325.2	c.437C>T	p.Thr146Met	missense_variant	7/12
BCAT2	NM_001164773.2	c.281C>T	p.Thr94Met	missense_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCAT2	ENST00000316273.11	c.557C>T	p.Thr186Met	missense_variant	6/11	1	NM_001190.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1406100 Hom.: 0 Cov.: 33 AF XY: 0.00000144 AC XY: 1 AN XY: 694216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	20
Dann	Uncertain	1.0
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.96	D;.;D;D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.7	D;D;D;.;.;.;.
REVEL	Benign	0.066
Sift	Benign	0.086	T;T;D;.;.;.;.
Sift4G	Benign	0.094	T;T;T;T;T;T;T
Polyphen		0.35	B;D;D;.;D;.;.
Vest4		0.33
MutPred		0.32		.;.;Loss of catalytic residue at T186 (P = 0.0892);.;.;.;Loss of catalytic residue at T186 (P = 0.0892);
MVP		0.48
MPC		0.53
ClinPred		0.53	D
GERP RS		2.0
Varity_R		0.11
gMVP		0.48

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

LitVar

Other links and lift over

dbSNP: rs11548193; hg19: chr19-49303070;