5-77776242-C-T

Variant names:

• chr5-77776242-C-T
• rs142821556
• NM_004607.3:c.16G>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.16G>A​(p.Val6Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V6L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBCA NM_004607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 2 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: 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=0.1579335).

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.16G>A	p.Val6Met	missense	Exon 1 of 4	NP_004598.1	O75347-1
	TBCA	NM_001297738.2		c.16G>A	p.Val6Met	missense	Exon 1 of 3	NP_001284667.1	O75347-2
	TBCA	NM_001297740.2		c.16G>A	p.Val6Met	missense	Exon 1 of 3	NP_001284669.1	E5RIX8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCA	ENST00000380377.9	TSL:1 MANE Select	c.16G>A	p.Val6Met	missense	Exon 1 of 4	ENSP00000369736.4	O75347-1
	TBCA	ENST00000518338.6	TSL:2	c.16G>A	p.Val6Met	missense	Exon 1 of 5	ENSP00000429793.2	E5RHG6
	TBCA	ENST00000932729.1		c.16G>A	p.Val6Met	missense	Exon 1 of 5	ENSP00000602788.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1427160 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 706816

African (AFR) AF: 0.00 AC: 0 AN: 32644

American (AMR) AF: 0.00 AC: 0 AN: 40254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25580

East Asian (EAS) AF: 0.00 AC: 0 AN: 37716

South Asian (SAS) AF: 0.00 AC: 0 AN: 81340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4118

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095650

Other (OTH) AF: 0.00 AC: 0 AN: 58954

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.036
Sift	Benign	0.060	T
Sift4G	Uncertain	0.0070	D
Polyphen		0.039	B
Vest4		0.30
MutPred		0.26		Loss of sheet (P = 0.0817)
MVP		0.23
MPC		0.38
ClinPred		0.91	D
GERP RS		3.9
PromoterAI		-0.074	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.46
Mutation Taster		=74/26	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: rs142821556; hg19: chr5-77072066;