17-82942462-GA-AG

Variant names:

• chr17-82942462-GA-AG
• NM_005993.5:c.3578_3579delGAinsAG
• TBCD p.1194

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The NM_005993.5(TBCD):​c.3578_3579delGAinsAG​(p.1194) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TBCD NM_005993.5 stop_retained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• Publications: 0 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=2.41 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005993.5. 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
	TBCD	NM_005993.5	MANE Select	c.3578_3579delGAinsAG	p.1194	stop_retained	N/A	NP_005984.3
	QTGAL	NM_001009905.3	MANE Select	c.*1611_*1612delTCinsCT		3_prime_UTR	Exon 13 of 13	NP_001009905.2	Q67FW5
	TBCD	NM_001411101.1		c.3527_3528delGAinsAG	p.1177	stop_retained	N/A	NP_001398030.1	A0A804HLI2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCD	ENST00000355528.9	TSL:1 MANE Select	c.3578_3579delGAinsAG	p.1194	stop_retained	N/A	ENSP00000347719.4	Q9BTW9-1
	B3GNTL1	ENST00000320865.4	TSL:1 MANE Select	c.*1611_*1612delTCinsCT		3_prime_UTR	Exon 13 of 13	ENSP00000319979.4	Q67FW5
	TBCD	ENST00000576677.6	TSL:1	n.3728_3729delGAinsAG		non_coding_transcript_exon	Exon 16 of 16

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4

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: chr17-80900338;