rs3785513

chr17-82928872-G-Achr17-82928872-G-T

Variant summary

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

The NM_005993.5(TBCD):c.2694-241G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,968 control chromosomes in the GnomAD database, including 11,011 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 0.36 (11011 hom., cov: 32)
• Consequence: TBCD NM_005993.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBCD	NM_005993.5	c.2694-241G>A		intron_variant		ENST00000355528.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCD	ENST00000355528.9	c.2694-241G>A		intron_variant		1	NM_005993.5	P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55054 AN: 151850 Hom.: 10974 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.363 AC: 55147 AN: 151968 Hom.: 11011 Cov.: 32 AF XY: 0.362 AC XY: 26916 AN XY: 74282

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.373

Alfa AF: 0.332 Hom.: 1487

Bravo AF: 0.374

Asia WGS AF: 0.374 AC: 1300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.6
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3785513; hg19: chr17-80886748;