rs354596

chr5-77839018-A-G

Variant summary

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

The ENST00000522370.1(TBCA):c.-20+29616T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 152,338 control chromosomes in the GnomAD database, including 453 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 0.052 (453 hom., cov: 33)
• Consequence: TBCA ENST00000522370.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

Genes affected

TBCA (HGNC:11579): (tubulin folding cofactor A) The product of this gene 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. This gene encodes chaperonin cofactor A. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCA	ENST00000522370.1	c.-20+29616T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7877 AN: 152220 Hom.: 451 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0377

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

GnomAD4 genome AF: 0.0519 AC: 7907 AN: 152338 Hom.: 453 Cov.: 33 AF XY: 0.0505 AC XY: 3760 AN XY: 74498

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0253

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.0168

Gnomad4 OTH AF: 0.0373

Alfa AF: 0.0414 Hom.: 77

Bravo AF: 0.0562

Asia WGS AF: 0.0180 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.6
Dann	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs354596; hg19: chr5-77134842;