rs121965003

Variant names:

• chr1-100216174-G-A
• NM_001918.5:c.581C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-100216174-G-A
• chr1-100216174-G-C
• chr1-100216174-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001918.5(DBT):​c.581C>T​(p.Ser194Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,270 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DBT NM_001918.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBT	NM_001918.5	c.581C>T	p.Ser194Leu	missense_variant	Exon 6 of 11	ENST00000370132.8	NP_001909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBT	ENST00000370132.8	c.581C>T	p.Ser194Leu	missense_variant	Exon 6 of 11	1	NM_001918.5	ENSP00000359151.3
DBT	ENST00000370131.3	c.581C>T	p.Ser194Leu	missense_variant	Exon 6 of 8	1		ENSP00000359150.3
DBT	ENST00000681617.1	c.581C>T	p.Ser194Leu	missense_variant	Exon 6 of 12			ENSP00000505544.1
DBT	ENST00000681780.1	c.38C>T	p.Ser13Leu	missense_variant	Exon 7 of 12			ENSP00000505780.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461270 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726984

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: 0.0000187

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	.;D
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.45	T
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Vest4		0.44
MutPred		0.78		Loss of disorder (P = 0.039);Loss of disorder (P = 0.039);
MVP		0.57
MPC		0.52
ClinPred		0.99	D
GERP RS		4.9
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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.

Other links and lift over

hg19: chr1-100681730;