rs672601248

Variant names:

• chr3-15645083-GGGAAAGGAAGGCTA-NNNNNNNNNNN
• NM_001370658.1:c.1167_1181delGGGAAAGGAAGGCTAinsNNNNNNNNNNN

Your query was ambiguous. Multiple possible variants found:

• chr3-15645082-GGGGAAAGGAAGGCTA-GNNNNNNNNNNN
• chr3-15645082-GGGGAAAGGAAGGCTA-GTTCCAATGGCC

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1 PP2

The NM_001370658.1(BTD):​c.1167_1181delGGGAAAGGAAGGCTAinsNNNNNNNNNNN​(p.Trp389fs) variant causes a frameshift, missense change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 N/A (N/A hom., cov:)
  • Exomes 𝑓: N/A (N/A hom.)
• Consequence: BTD NM_001370658.1 frameshift, missense
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned
• Publications: 0 publications found

Genes affected

BTD (HGNC:1122): (biotinidase) The protein encoded by this gene functions to recycle protein-bound biotin by cleaving biocytin (biotin-epsilon-lysine), a normal product of carboxylase degradation, resulting in regeneration of free biotin. The encoded protein has also been shown to have biotinyl transferase activity. Mutations in this gene are associated with biotinidase deficiency. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Aug 2013]

BTD Gene-Disease associations (from GenCC):

• biotinidase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, ClinGen, Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 82 pathogenic variants in the truncated region.
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 88 curated pathogenic missense variants (we use a threshold of 10). The gene has 9 curated benign missense variants. Gene score misZ: -0.52516 (below the threshold of 3.09). Trascript score misZ: 0.15371 (below the threshold of 3.09). GenCC associations: The gene is linked to Leigh syndrome, biotinidase deficiency.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTD	NM_001370658.1	c.1167_1181delGGGAAAGGAAGGCTAinsNNNNNNNNNNN	p.Trp389fs	frameshift_variant, missense_variant	Exon 4 of 4	ENST00000643237.3	NP_001357587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTD	ENST00000643237.3	c.1167_1181delGGGAAAGGAAGGCTAinsNNNNNNNNNNN	p.Trp389fs	frameshift_variant, missense_variant	Exon 4 of 4		NM_001370658.1	ENSP00000495254.2

Frequencies

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr3-15686590;