chr5-77839018-A-G

Variant names:

• chr5-77839018-A-G
• rs354596
• ENST00000522370.1:c.-20+29616T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCA	ENST00000522370.1	c.-20+29616T>C		intron_variant	Intron 1 of 3	3		ENSP00000429313.1

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

African (AFR) AF: 0.145 AC: 6032 AN: 41558

American (AMR) AF: 0.0253 AC: 388 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3466

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.0199 AC: 96 AN: 4830

European-Finnish (FIN) AF: 0.0138 AC: 147 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0168 AC: 1145 AN: 68040

Other (OTH) AF: 0.0373 AC: 79 AN: 2116

Alfa AF: 0.0367 Hom.: 108

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
PhyloP100		-0.056
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs354596; hg19: chr5-77134842;