12-24832725-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_005504.7(BCAT1):c.1042G>A(p.Glu348Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00514 in 1,603,164 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0039 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 23 hom. )

Consequence

BCAT1
NM_005504.7 missense, splice_region

Scores

Splicing: ADA: 0.00007754

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.385

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:

ENSG00000256482 (HGNC:58192):

ENSG00000256482 links:

LOC105369699 (HGNC:):

LOC105369699 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003926307).

BP6

Variant 12-24832725-C-T is Benign according to our data. Variant chr12-24832725-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3033269.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAT1	NM_005504.7 link	c.1042G>A	p.Glu348Lys	missense_variant, splice_region_variant	Exon 9 of 11	ENST00000261192.12	NP_005495.2	P54687-1A0A024RAV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAT1	ENST00000261192.12 link	c.1042G>A	p.Glu348Lys	missense_variant, splice_region_variant	Exon 9 of 11	1	NM_005504.7	ENSP00000261192.7		P54687-1

Frequencies

GnomAD3 genomes

AF:

0.00391

AC:

595

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00663

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00421

AC:

1003

AN:

238008

Hom.:

AF XY:

0.00433

AC XY:

558

AN XY:

128764

show subpopulations

Gnomad AFR exome

AF:

0.000807

Gnomad AMR exome

AF:

0.00143

Gnomad ASJ exome

AF:

0.00311

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00347

Gnomad FIN exome

AF:

0.00387

Gnomad NFE exome

AF:

0.00652

Gnomad OTH exome

AF:

0.00480

GnomAD4 exome

AF:

0.00527

AC:

7650

AN:

1450854

Hom.:

Cov.:

AF XY:

0.00519

AC XY:

3743

AN XY:

720984

show subpopulations

Gnomad4 AFR exome

AF:

0.00103

Gnomad4 AMR exome

AF:

0.00171

Gnomad4 ASJ exome

AF:

0.00288

Gnomad4 EAS exome

AF:

0.0000759

Gnomad4 SAS exome

AF:

0.00365

Gnomad4 FIN exome

AF:

0.00379

Gnomad4 NFE exome

AF:

0.00605

Gnomad4 OTH exome

AF:

0.00412

GnomAD4 genome

AF:

0.00391

AC:

595

AN:

152310

Hom.:

Cov.:

AF XY:

0.00354

AC XY:

264

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.00663

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00584

Hom.:

Bravo

AF:

0.00357

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00665

AC:

ExAC

AF:

0.00403

AC:

487

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BCAT1-related disorder

Benign:1

Mar 03, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.25

T;.;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.090

LIST_S2

Uncertain

0.90

D;D;D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.0039

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.23

N;.;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.49

N;N;N;N;N

REVEL

Benign

0.062

Sift

Benign

0.53

T;T;T;T;T

Sift4G

Benign

0.73

T;T;T;T;T

Polyphen

0.0040

B;.;.;.;.

Vest4

0.13

MVP

0.15

MPC

0.024

ClinPred

0.0056

GERP RS

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000078

dbscSNV1_RF

Benign

0.0020

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over