12-24832725-C-T

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

1
18
Splicing: ADA: 0.00007754
2

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]

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
BCAT1NM_005504.7 linkc.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
BCAT1ENST00000261192.12 linkc.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.:
1
Cov.:
32
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.:
3
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.:
23
Cov.:
31
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.:
1
Cov.:
32
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.:
6
Bravo
AF:
0.00357
TwinsUK
AF:
0.00485
AC:
18
ALSPAC
AF:
0.00467
AC:
18
ESP6500AA
AF:
0.000782
AC:
3
ESP6500EA
AF:
0.00665
AC:
55
ExAC
AF:
0.00403
AC:
487
Asia WGS
AF:
0.00231
AC:
8
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
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
16
DANN
Benign
0.72
DEOGEN2
Benign
0.25
T;.;.;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.090
N
LIST_S2
Uncertain
0.90
D;D;D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.0039
T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.23
N;.;.;.;.
PrimateAI
Benign
0.32
T
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
T
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.

Other links and lift over

dbSNP: rs144632372; hg19: chr12-24985659; API