rs142821556

Variant names:

• chr5-77776242-C-G
• rs142821556
• NM_004607.3:c.16G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-77776242-C-G
• chr5-77776242-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004607.3(TBCA):​c.16G>C​(p.Val6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000677 in 1,579,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000070 (0 hom.)
• Consequence: TBCA NM_004607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045512408).

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>C	p.Val6Leu	missense	Exon 1 of 4	NP_004598.1	O75347-1
	TBCA	NM_001297738.2		c.16G>C	p.Val6Leu	missense	Exon 1 of 3	NP_001284667.1	O75347-2
	TBCA	NM_001297740.2		c.16G>C	p.Val6Leu	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>C	p.Val6Leu	missense	Exon 1 of 4	ENSP00000369736.4	O75347-1
	TBCA	ENST00000518338.6	TSL:2	c.16G>C	p.Val6Leu	missense	Exon 1 of 5	ENSP00000429793.2	E5RHG6
	TBCA	ENST00000932729.1		c.16G>C	p.Val6Leu	missense	Exon 1 of 5	ENSP00000602788.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000509 AC: 10 AN: 196624 AF XY: 0.0000190

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000118

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000701 AC: 100 AN: 1427160 Hom.: 0 Cov.: 31 AF XY: 0.0000594 AC XY: 42 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: 0.0000123 AC: 1 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: 0.0000867 AC: 95 AN: 1095650

Other (OTH) AF: 0.0000678 AC: 4 AN: 58954

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74378

African (AFR) AF: 0.0000482 AC: 2 AN: 41468

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.0000529

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000834 AC: 1

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	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.0	N
PhyloP100		1.1
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.17	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.24		Loss of sheet (P = 0.0817)
MVP		0.14
MPC		0.37
ClinPred		0.14	T
GERP RS		3.9
PromoterAI		-0.050	Neutral
Varity_R		0.18
gMVP		0.52
Mutation Taster		=78/22	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;