NM_001190.4:c.1147A>G

Variant names:

• chr19-48795458-T-C
• rs145231743
• NM_001190.4:c.1147A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001190.4(BCAT2):​c.1147A>G​(p.Ile383Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. I383F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BCAT2 NM_001190.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.08
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048887283).

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.1147A>G	p.Ile383Val	missense	Exon 11 of 11	NP_001181.2	O15382-1
	BCAT2	NM_001284325.2		c.1027A>G	p.Ile343Val	missense	Exon 12 of 12	NP_001271254.1	B3KSI3
	BCAT2	NM_001164773.2		c.871A>G	p.Ile291Val	missense	Exon 9 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.1147A>G	p.Ile383Val	missense	Exon 11 of 11	ENSP00000322991.5	O15382-1
	BCAT2	ENST00000545387.6	TSL:1	c.871A>G	p.Ile291Val	missense	Exon 9 of 9	ENSP00000440973.1	O15382-2
	BCAT2	ENST00000593515.5	TSL:5	c.1306A>G	p.Ile436Val	missense	Exon 11 of 11	ENSP00000469139.1	M0QXF9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461658 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727106

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111948

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.9
DANN	Benign	0.79
DEOGEN2	Benign	0.22	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.035	N
PhyloP100		-1.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.013
Sift	Benign	0.33	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.061
MutPred		0.35		Gain of MoRF binding (P = 0.1235)
MVP		0.18
MPC		0.33
ClinPred		0.13	T
GERP RS		-3.3
Varity_R		0.19
gMVP		0.66
Mutation Taster		=88/12	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: rs145231743; hg19: chr19-49298715;