rs138253411

Variant names:

• chr19-48796614-C-G
• rs138253411
• NM_001190.4:c.1029G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-48796614-C-G
• chr19-48796614-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001190.4(BCAT2):​c.1029G>C​(p.Gln343His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q343Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BCAT2 NM_001190.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449
• Publications: 0 publications found

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]

BCAT2 Gene-Disease associations (from GenCC):

• hypervalinemia and hyperleucine-isoleucinemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAT2	NM_001190.4	MANE Select	c.1029G>C	p.Gln343His	missense	Exon 9 of 11	NP_001181.2	O15382-1
	BCAT2	NM_001284325.2		c.909G>C	p.Gln303His	missense	Exon 10 of 12	NP_001271254.1	B3KSI3
	BCAT2	NM_001164773.2		c.753G>C	p.Gln251His	missense	Exon 7 of 9	NP_001158245.1	O15382-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAT2	ENST00000316273.11	TSL:1 MANE Select	c.1029G>C	p.Gln343His	missense	Exon 9 of 11	ENSP00000322991.5	O15382-1
	BCAT2	ENST00000598162.5	TSL:1	c.1029G>C	p.Gln343His	missense	Exon 9 of 10	ENSP00000470216.1	M0QZ10
	BCAT2	ENST00000599246.5	TSL:1	c.753G>C	p.Gln251His	missense	Exon 7 of 8	ENSP00000470680.1	M0QZP4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.029
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.45
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.92	P
Vest4		0.54
MutPred		0.61		Loss of sheet (P = 0.0817)
MVP		0.48
MPC		0.97
ClinPred		0.95	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.72
gMVP		0.89
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs138253411; hg19: chr19-49299871;