ENST00000522370.1:c.-20+5062C>T

Variant names:

• chr5-77863572-G-A
• rs10514124
• ENST00000522370.1:c.-20+5062C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

ENSG00000296090 (HGNC:):

ACMG classification

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCA	ENST00000522370.1	c.-20+5062C>T		intron_variant	Intron 1 of 3	3		ENSP00000429313.1
ENSG00000296090	ENST00000736338.1	n.90-10294G>A		intron_variant	Intron 1 of 2
ENSG00000296090	ENST00000736339.1	n.69-10294G>A		intron_variant	Intron 1 of 3
ENSG00000296090	ENST00000736340.1	n.85-10294G>A		intron_variant	Intron 1 of 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

African (AFR) AF: 0.112 AC: 4631 AN: 41472

American (AMR) AF: 0.258 AC: 3941 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1377 AN: 3470

East Asian (EAS) AF: 0.183 AC: 947 AN: 5172

South Asian (SAS) AF: 0.245 AC: 1180 AN: 4820

European-Finnish (FIN) AF: 0.377 AC: 3984 AN: 10578

Middle Eastern (MID) AF: 0.403 AC: 117 AN: 290

European-Non Finnish (NFE) AF: 0.338 AC: 22971 AN: 67994

Other (OTH) AF: 0.301 AC: 635 AN: 2112

Alfa AF: 0.321 Hom.: 33425

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
PhyloP100		-0.21
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: rs10514124; hg19: chr5-77159396;