17-82864204-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005993.5(TBCD):c.1319-6020A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,234 control chromosomes in the GnomAD database, including 4,866 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (4866 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: TBCD NM_005993.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBCD	NM_005993.5	c.1319-6020A>G		intron_variant		ENST00000355528.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCD	ENST00000355528.9	c.1319-6020A>G		intron_variant		1	NM_005993.5	P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38423 AN: 152096 Hom.: 4870 Cov.: 33

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.250 AC: 5 AN: 20 Hom.: 0 AF XY: 0.167 AC XY: 2 AN XY: 12

Gnomad4 AFR exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.252 AC: 38424 AN: 152214 Hom.: 4866 Cov.: 33 AF XY: 0.251 AC XY: 18695 AN XY: 74422

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.264

Alfa AF: 0.233 Hom.: 1978

Bravo AF: 0.256

Asia WGS AF: 0.244 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.6
Dann	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs733342; hg19: chr17-80822080;