rs10514124

Positions:

• chr5-77863572-G-A

Variant summary

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

The ENST00000522370.1(TBCA):​c.-20+5062C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,092 control chromosomes in the GnomAD database, including 6,047 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 0.26 (6047 hom., cov: 32)
• Consequence: TBCA ENST00000522370.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

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]

(HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.77863572G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCA	ENST00000522370.1	c.-20+5062C>T		intron_variant		3		ENSP00000429313.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39948 AN: 151974 Hom.: 6044 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.263 AC: 39957 AN: 152092 Hom.: 6047 Cov.: 32 AF XY: 0.263 AC XY: 19564 AN XY: 74360

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.301

Alfa AF: 0.338 Hom.: 17226

Bravo AF: 0.248

Asia WGS AF: 0.229 AC: 799 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	6.6
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10514124; hg19: chr5-77159396;