rs201117345

Variant names:

• chr1-100206304-ATT-A
• rs201117345
• NM_001918.5:c.1210-5_1210-4delAA

Your query was ambiguous. Multiple possible variants found:

• chr1-100206304-ATT-A
• chr1-100206304-ATT-AT
• chr1-100206304-ATT-ATTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001918.5(DBT):​c.1210-5_1210-4delAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,289,922 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: DBT NM_001918.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• maple syrup urine disease

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• maple syrup urine disease type 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health, G2P
• classic maple syrup urine disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intermediate maple syrup urine disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intermittent maple syrup urine disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• thiamine-responsive maple syrup urine disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285530 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBT	NM_001918.5	c.1210-5_1210-4delAA		splice_region_variant, intron_variant	Intron 9 of 10	ENST00000370132.8	NP_001909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBT	ENST00000370132.8	c.1210-5_1210-4delAA		splice_region_variant, intron_variant	Intron 9 of 10	1	NM_001918.5	ENSP00000359151.3
DBT	ENST00000681617.1	c.1336-5_1336-4delAA		splice_region_variant, intron_variant	Intron 10 of 11			ENSP00000505544.1
DBT	ENST00000681780.1	c.667-5_667-4delAA		splice_region_variant, intron_variant	Intron 10 of 11			ENSP00000505780.1
ENSG00000285530	ENST00000835180.1	n.140-12339_140-12338delTT		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000870 AC: 17 AN: 195454 AF XY: 0.0000661

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000417

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000633

Gnomad FIN exome AF: 0.0000564

Gnomad NFE exome AF: 0.0000233

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 23 AN: 1289922 Hom.: 0 AF XY: 0.0000248 AC XY: 16 AN XY: 644166

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31952

American (AMR) AF: 0.00 AC: 0 AN: 39640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23452

East Asian (EAS) AF: 0.00 AC: 0 AN: 36494

South Asian (SAS) AF: 0.000190 AC: 15 AN: 79018

European-Finnish (FIN) AF: 0.0000213 AC: 1 AN: 47030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5346

European-Non Finnish (NFE) AF: 0.00000617 AC: 6 AN: 973164

Other (OTH) AF: 0.0000186 AC: 1 AN: 53826

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

Alfa AF: 0.0000479 Hom.: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.56
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs201117345; hg19: chr1-100671860;