12-24818019-C-T

Variant names:

• chr12-24818019-C-T
• rs748490658
• NM_005504.7:c.1150G>A

Variant summary

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

The NM_005504.7(BCAT1):​c.1150G>A​(p.Val384Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. V384L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BCAT1 NM_005504.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 0 publications found

Genes affected

BCAT1 (HGNC:976): (branched chain amino acid transaminase 1) This gene encodes the cytosolic form of the enzyme branched-chain amino acid transaminase. This enzyme catalyzes the reversible transamination of branched-chain alpha-keto acids to branched-chain L-amino acids essential for cell growth. Two different clinical disorders have been attributed to a defect of branched-chain amino acid transamination: hypervalinemia and hyperleucine-isoleucinemia. As there is also a gene encoding a mitochondrial form of this enzyme, mutations in either gene may contribute to these disorders. Alternatively spliced transcript variants have been described. [provided by RefSeq, May 2010]

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=0.062183112).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005504.7. 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
	BCAT1	NM_005504.7	MANE Select	c.1150G>A	p.Val384Met	missense	Exon 11 of 11	NP_005495.2
	BCAT1	NM_001413087.1		c.1222G>A	p.Val408Met	missense	Exon 11 of 11	NP_001400016.1
	BCAT1	NM_001413088.1		c.1213G>A	p.Val405Met	missense	Exon 12 of 12	NP_001400017.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAT1	ENST00000261192.12	TSL:1 MANE Select	c.1150G>A	p.Val384Met	missense	Exon 11 of 11	ENSP00000261192.7	P54687-1
	BCAT1	ENST00000538118.5	TSL:1	c.1147G>A	p.Val383Met	missense	Exon 11 of 11	ENSP00000440817.1	P54687-4
	BCAT1	ENST00000539282.5	TSL:2	c.1186G>A	p.Val396Met	missense	Exon 11 of 11	ENSP00000443459.1	P54687-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460788 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726658

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111368

Other (OTH) AF: 0.00 AC: 0 AN: 60308

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.8
DANN	Benign	0.97
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.016	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-1.4
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.022
Sift	Benign	0.039	D
Sift4G	Benign	0.096	T
Polyphen		0.0010	B
Vest4		0.043
MutPred		0.36		Gain of disorder (P = 0.1115)
MVP		0.10
MPC		0.023
ClinPred		0.11	T
GERP RS		-0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.053
gMVP		0.58
Mutation Taster		=81/19	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: rs748490658; hg19: chr12-24970953;