TBCD p.Ter1193Ter

Variant names:

• chr17-82942460-C-C
• NM_001009905.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr17-82942461--
• chr17-82942462-G-A
• chr17-82942462-GA-AG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001009905.3(QTGAL):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: QTGAL NM_001009905.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• Publications: 0 publications found

Genes affected

QTGAL (HGNC:21727): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase like 1) Predicted to enable glycosyltransferase activity. [provided by Alliance of Genome Resources, Apr 2022]

TBCD (HGNC:11581): (tubulin folding cofactor D) Cofactor D is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. [provided by RefSeq, Jul 2008]

TBCD Gene-Disease associations (from GenCC):

• early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009905.3. 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
	QTGAL	NM_001009905.3	MANE Select	c.		exon_region	Exon 13 of 13	NP_001009905.2	Q67FW5
	QTGAL	NM_001009905.3	MANE Select	c.		3_prime_UTR	Exon 13 of 13	NP_001009905.2	Q67FW5
	QTGAL	NM_001320742.2		c.		exon_region	Exon 14 of 14	NP_001307671.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GNTL1	ENST00000320865.4	TSL:1 MANE Select	c.		exon_region	Exon 13 of 13	ENSP00000319979.4	Q67FW5
	B3GNTL1	ENST00000320865.4	TSL:1 MANE Select	c.		3_prime_UTR	Exon 13 of 13	ENSP00000319979.4	Q67FW5
	B3GNTL1	ENST00000572977.5	TSL:2	n.		exon_region	Exon 10 of 10	ENSP00000459327.1	I3L232

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-80900336;