chr1-100187702-T-TA

Variant names:

• chr1-100187702-T-TA
• rs886044939
• NM_001918.5:c.*8552_*8553insT

Variant summary

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

The NM_001918.5(DBT):​c.*8552_*8553insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DBT NM_001918.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.412
• Publications: 0 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: G2P, Myriad Women’s Health
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001918.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBT	NM_001918.5	MANE Select	c.*8552_*8553insT		3_prime_UTR	Exon 11 of 11	NP_001909.4	P11182
	DBT	NM_001399969.1		c.*8552_*8553insT		3_prime_UTR	Exon 12 of 12	NP_001386898.1	A0A7P0T9W1
	DBT	NM_001399972.1		c.*8552_*8553insT		3_prime_UTR	Exon 12 of 12	NP_001386901.1	A0A7P0T9W1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBT	ENST00000370132.8	TSL:1 MANE Select	c.*8552_*8553insT		3_prime_UTR	Exon 11 of 11	ENSP00000359151.3	P11182
	DBT	ENST00000875462.1		c.*42-4576_*42-4575insT		intron	N/A	ENSP00000545521.1
	ENSG00000285530	ENST00000835180.1		n.139+20759_139+20760insA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000690 AC: 1 AN: 144870 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000153

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000690 AC: 1 AN: 144870 Hom.: 0 Cov.: 32 AF XY: 0.0000142 AC XY: 1 AN XY: 70586

African (AFR) AF: 0.00 AC: 0 AN: 40238

American (AMR) AF: 0.00 AC: 0 AN: 14444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3384

East Asian (EAS) AF: 0.00 AC: 0 AN: 4970

South Asian (SAS) AF: 0.00 AC: 0 AN: 4604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65226

Other (OTH) AF: 0.00 AC: 0 AN: 1922

Alfa AF: 0.000224 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Maple syrup urine disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.41

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: rs886044939; hg19: chr1-100653258;