NM_001363644.2:c.578G>A

Variant names:

• chr11-121055174-G-A
• rs1301403335
• NM_001363644.2:c.578G>A

Variant summary

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

The NM_001363644.2(TBCEL):​c.578G>A​(p.Arg193Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TBCEL NM_001363644.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.98
• Publications: 0 publications found

Genes affected

TBCEL (HGNC:28115): (tubulin folding cofactor E like) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in microtubule cytoskeleton organization; post-chaperonin tubulin folding pathway; and tubulin complex assembly. Predicted to be located in cytoskeleton. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TBCEL-TECTA (HGNC:54857): (TBCEL-TECTA readthrough) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in microtubule cytoskeleton organization; post-chaperonin tubulin folding pathway; and tubulin complex assembly. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363644.2. 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
	TBCEL	NM_001363644.2	MANE Select	c.578G>A	p.Arg193Gln	missense	Exon 6 of 9	NP_001350573.1	Q5QJ74
	TBCEL-TECTA	NM_001378761.1		c.578G>A	p.Arg193Gln	missense	Exon 5 of 30	NP_001365690.1
	TBCEL	NM_001130047.3		c.578G>A	p.Arg193Gln	missense	Exon 5 of 8	NP_001123519.1	Q5QJ74

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCEL	ENST00000683345.1	MANE Select	c.578G>A	p.Arg193Gln	missense	Exon 6 of 9	ENSP00000507873.1	Q5QJ74
	TBCEL-TECTA	ENST00000645041.1		c.530G>A	p.Arg177Gln	missense	Exon 4 of 10	ENSP00000496315.1	A0A2R8YFB7
	TBCEL	ENST00000422003.6	TSL:1	c.578G>A	p.Arg193Gln	missense	Exon 5 of 8	ENSP00000403925.2	Q5QJ74

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151736 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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.: 31

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151736 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74096

African (AFR) AF: 0.0000242 AC: 1 AN: 41340

American (AMR) AF: 0.00 AC: 0 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67850

Other (OTH) AF: 0.00 AC: 0 AN: 2084

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	0.092
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.034	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		8.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.22
Sift	Benign	0.084	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.43
MutPred		0.56		Gain of ubiquitination at K194 (P = 0.0872)
MVP		0.67
MPC		1.8
ClinPred		0.90	D
GERP RS		5.0
Varity_R		0.20
gMVP		0.55
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1301403335; hg19: chr11-120925883; COSMIC: COSV105115534;