NM_004607.3:c.252T>A

Variant names:

• chr5-77691493-A-T
• rs1745748381
• NM_004607.3:c.252T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004607.3(TBCA):​c.252T>A​(p.Asn84Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TBCA NM_004607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.43
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20031169).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004607.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCA	NM_004607.3	MANE Select	c.252T>A	p.Asn84Lys	missense	Exon 4 of 4	NP_004598.1	O75347-1
	TBCA	NM_001297740.2		c.165T>A	p.Asn55Lys	missense	Exon 3 of 3	NP_001284669.1	E5RIX8
	TBCA	NM_001297738.2		c.*1629T>A		3_prime_UTR	Exon 3 of 3	NP_001284667.1	O75347-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCA	ENST00000380377.9	TSL:1 MANE Select	c.252T>A	p.Asn84Lys	missense	Exon 4 of 4	ENSP00000369736.4	O75347-1
	TBCA	ENST00000518338.6	TSL:2	c.321T>A	p.Asn107Lys	missense	Exon 5 of 5	ENSP00000429793.2	E5RHG6
	TBCA	ENST00000932729.1		c.321T>A	p.Asn107Lys	missense	Exon 5 of 5	ENSP00000602788.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 28

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152098 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.97
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.4
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.13
Sift	Benign	0.56	T
Sift4G	Benign	0.73	T
Polyphen		0.014	B
Vest4		0.14
MutPred		0.42		Gain of ubiquitination at N84 (P = 0.0031)
MVP		0.42
MPC		0.44
ClinPred		0.76	D
GERP RS		4.6
Varity_R		0.32
Mutation Taster		=63/37	polymorphism

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: rs1745748381; hg19: chr5-76987318;