rs353951

Positions:

• chr5-77802745-A-G
• chr5-77802745-A-T

Variant summary

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

The ENST00000522370.1(TBCA):​c.-20+65889T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,080 control chromosomes in the GnomAD database, including 16,448 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 0.46 (16448 hom., cov: 33)
• Consequence: TBCA ENST00000522370.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.517 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+65889T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69996 AN: 151962 Hom.: 16439 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.461 AC: 70039 AN: 152080 Hom.: 16448 Cov.: 33 AF XY: 0.462 AC XY: 34311 AN XY: 74322

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.447

Alfa AF: 0.490 Hom.: 3587

Bravo AF: 0.457

Asia WGS AF: 0.452 AC: 1569 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	1.3
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs353951; hg19: chr5-77098569;