chr5-77694254-A-G

Variant names:

• chr5-77694254-A-G
• rs455742
• NM_004607.3:c.160-902T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004607.3(TBCA):​c.160-902T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,036 control chromosomes in the GnomAD database, including 24,276 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 0.56 (24276 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: TBCA NM_004607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• 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]

ENSG00000305113 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCA	NM_004607.3	c.160-902T>C		intron_variant	Intron 2 of 3	ENST00000380377.9	NP_004598.1
TBCA	NM_001297738.2	c.160-902T>C		intron_variant	Intron 2 of 2		NP_001284667.1
TBCA	NM_001297740.2	c.160-2756T>C		intron_variant	Intron 2 of 2		NP_001284669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCA	ENST00000380377.9	c.160-902T>C		intron_variant	Intron 2 of 3	1	NM_004607.3	ENSP00000369736.4

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85495 AN: 151918 Hom.: 24260 Cov.: 33

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.583

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.563 AC: 85558 AN: 152036 Hom.: 24276 Cov.: 33 AF XY: 0.563 AC XY: 41868 AN XY: 74310

African (AFR) AF: 0.614 AC: 25444 AN: 41466

American (AMR) AF: 0.500 AC: 7637 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2370 AN: 3468

East Asian (EAS) AF: 0.470 AC: 2425 AN: 5162

South Asian (SAS) AF: 0.661 AC: 3182 AN: 4814

European-Finnish (FIN) AF: 0.518 AC: 5465 AN: 10556

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37108 AN: 67988

Other (OTH) AF: 0.582 AC: 1229 AN: 2112

Alfa AF: 0.549 Hom.: 2963

Bravo AF: 0.561

Asia WGS AF: 0.560 AC: 1945 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Benign	0.82
PhyloP100		2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs455742; hg19: chr5-76990079;