chr19-48796614-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001190.4(BCAT2):​c.1029G>A​(p.Gln343Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: BCAT2 NM_001190.4 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=0.449 with no splicing effect.

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>A	p.Gln343Gln	synonymous	Exon 9 of 11	NP_001181.2	O15382-1
	BCAT2	NM_001284325.2		c.909G>A	p.Gln303Gln	synonymous	Exon 10 of 12	NP_001271254.1	B3KSI3
	BCAT2	NM_001164773.2		c.753G>A	p.Gln251Gln	synonymous	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>A	p.Gln343Gln	synonymous	Exon 9 of 11	ENSP00000322991.5	O15382-1
	BCAT2	ENST00000598162.5	TSL:1	c.1029G>A	p.Gln343Gln	synonymous	Exon 9 of 10	ENSP00000470216.1	M0QZ10
	BCAT2	ENST00000599246.5	TSL:1	c.753G>A	p.Gln251Gln	synonymous	Exon 7 of 8	ENSP00000470680.1	M0QZP4

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250652 AF XY: 0.00000737

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461408 Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4 AN XY: 727068

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44710

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52970

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152212 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74360

African (AFR) AF: 0.000121 AC: 5 AN: 41464

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

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
BayesDel_noAF	Benign	-0.47
CADD	Benign	4.9
DANN	Benign	0.78
PhyloP100		0.45

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;