Genetic Variant BCAT1:p.Thr165Ala (chr12-24878547-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005504.7(BCAT1):c.493A>G(p.Thr165Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,560 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BCAT1
NM_005504.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.03

Publications

0 publications found

Variant links:

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]

BCAT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2753546).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BCAT1	NM_005504.7	MANE Select	c.493A>G	p.Thr165Ala	missense	Exon 5 of 11	NP_005495.2
BCAT1	NM_001413086.1		c.529A>G	p.Thr177Ala	missense	Exon 5 of 12	NP_001400015.1
BCAT1	NM_001413087.1		c.565A>G	p.Thr189Ala	missense	Exon 5 of 11	NP_001400016.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCAT1	ENST00000261192.12	TSL:1 MANE Select	c.493A>G	p.Thr165Ala	missense	Exon 5 of 11	ENSP00000261192.7	P54687-1
BCAT1	ENST00000538118.5	TSL:1	c.490A>G	p.Thr164Ala	missense	Exon 5 of 11	ENSP00000440817.1	P54687-4
BCAT1	ENST00000544418.1	TSL:1	n.913A>G		non_coding_transcript_exon	Exon 5 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

246644

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

6.86e-7

AC:

AN:

1458560

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725568

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33342

American (AMR)

AF:

0.00

AC:

AN:

44056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110658

Other (OTH)

AF:

0.00

AC:

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.34

Eigen

Benign

-0.074

Eigen_PC

Benign

0.011

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

M_CAP

Benign

0.013

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

PhyloP100

4.0

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.13

Sift

Benign

0.030

Sift4G

Uncertain

0.041

Polyphen

0.043

Vest4

0.42

MutPred

0.50

Loss of phosphorylation at T165 (P = 0.0377)

MVP

0.21

MPC

0.025

ClinPred

0.82

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.63

gMVP

0.80

Mutation Taster

=32/68

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over