chr12-24832725-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 18/24 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

Publications

7 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:

BCAT1-AS1 (HGNC:58192):

BCAT1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3033269.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 23 AR gene

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.1042G>A	p.Glu348Lys	missense splice_region	Exon 9 of 11	NP_005495.2
BCAT1	NM_001413086.1		c.1078G>A	p.Glu360Lys	missense splice_region	Exon 9 of 12	NP_001400015.1
BCAT1	NM_001413087.1		c.1114G>A	p.Glu372Lys	missense splice_region	Exon 9 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.1042G>A	p.Glu348Lys	missense splice_region	Exon 9 of 11	ENSP00000261192.7	P54687-1
BCAT1	ENST00000538118.5	TSL:1	c.1039G>A	p.Glu347Lys	missense splice_region	Exon 9 of 11	ENSP00000440817.1	P54687-4
BCAT1	ENST00000539282.5	TSL:2	c.1078G>A	p.Glu360Lys	missense splice_region	Exon 9 of 11	ENSP00000443459.1	P54687-5

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

GnomAD2 exomes

AF:

0.00421

AC:

1003

AN:

238008

AF XY:

0.00433

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 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

African (AFR)

AF:

0.00103

AC:

AN:

33154

American (AMR)

AF:

0.00171

AC:

AN:

42730

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

25712

East Asian (EAS)

AF:

0.0000759

AC:

AN:

39530

South Asian (SAS)

AF:

0.00365

AC:

306

AN:

83818

European-Finnish (FIN)

AF:

0.00379

AC:

201

AN:

53086

Middle Eastern (MID)

AF:

0.00314

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00605

AC:

6694

AN:

1107150

Other (OTH)

AF:

0.00412

AC:

247

AN:

59936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

342

685

1027

1370

1712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00391

AC:

595

AN:

152310

Hom.:

Cov.:

AF XY:

0.00354

AC XY:

264

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

41568

American (AMR)

AF:

0.00183

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00358

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00663

AC:

451

AN:

68020

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

119

149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00538

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

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

BCAT1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.25

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.090

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.013

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.23

PhyloP100

0.39

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.49

REVEL

Benign

0.062

Sift

Benign

0.53

Sift4G

Benign

0.73

Polyphen

0.0040

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

Mutation Taster

=77/23

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over