dbSNP rs146249007: DBT:p.Ser242Ala (chr1-100216031-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001918.5(DBT):c.724T>G(p.Ser242Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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. S242P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DBT
NM_001918.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.899

Variant links:

Genes affected

DBT (HGNC:2698): (dihydrolipoamide branched chain transacylase E2) The branched-chain alpha-keto acid dehydrogenase complex (BCKD) is an inner-mitochondrial enzyme complex involved in the breakdown of the branched-chain amino acids isoleucine, leucine, and valine. The BCKD complex is thought to be composed of a core of 24 transacylase (E2) subunits, and associated decarboxylase (E1), dehydrogenase (E3), and regulatory subunits. This gene encodes the transacylase (E2) subunit. Mutations in this gene result in maple syrup urine disease, type 2. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

DBT links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057527274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBT	NM_001918.5 link	c.724T>G	p.Ser242Ala	missense_variant	Exon 6 of 11	ENST00000370132.8	NP_001909.4	P11182

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DBT	ENST00000370132.8 link	c.724T>G	p.Ser242Ala	missense_variant	Exon 6 of 11	1	NM_001918.5	ENSP00000359151.3	P11182
DBT	ENST00000370131.3 link	c.724T>G	p.Ser242Ala	missense_variant	Exon 6 of 8	1		ENSP00000359150.3	Q5VVL7
DBT	ENST00000681617.1 link	c.724T>G	p.Ser242Ala	missense_variant	Exon 6 of 12			ENSP00000505544.1	A0A7P0Z494
DBT	ENST00000681780.1 link	c.181T>G	p.Ser61Ala	missense_variant	Exon 7 of 12			ENSP00000505780.1	A0A7P0T9W1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461156

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.3

DANN

Benign

0.58

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.36

.;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.11

N;N

REVEL

Benign

0.028

Sift

Benign

0.68

T;T

Sift4G

Benign

0.83

T;T

Vest4

0.24

MutPred

0.18

Loss of glycosylation at S242 (P = 0.0182);Loss of glycosylation at S242 (P = 0.0182);

MVP

0.20

MPC

0.26

ClinPred

0.031

GERP RS

0.24

gMVP

0.31

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over