11-121045730-T-A

Variant names:

• chr11-121045730-T-A
• NM_001363644.2:c.40T>A

Variant summary

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

The NM_001363644.2(TBCEL):​c.40T>A​(p.Cys14Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBCEL NM_001363644.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08170882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCEL	NM_001363644.2	c.40T>A	p.Cys14Ser	missense_variant	Exon 3 of 9	ENST00000683345.1	NP_001350573.1
TBCEL-TECTA	NM_001378761.1	c.40T>A	p.Cys14Ser	missense_variant	Exon 2 of 30		NP_001365690.1
TBCEL	NM_001130047.3	c.40T>A	p.Cys14Ser	missense_variant	Exon 2 of 8		NP_001123519.1
TBCEL	NM_152715.5	c.40T>A	p.Cys14Ser	missense_variant	Exon 2 of 8		NP_689928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCEL	ENST00000683345.1	c.40T>A	p.Cys14Ser	missense_variant	Exon 3 of 9		NM_001363644.2	ENSP00000507873.1
TBCEL-TECTA	ENST00000645041.1	c.-9T>A		upstream_gene_variant				ENSP00000496315.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.40T>A (p.C14S) alteration is located in exon 2 (coding exon 1) of the TBCEL gene. This alteration results from a T to A substitution at nucleotide position 40, causing the cysteine (C) at amino acid position 14 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.50
DEOGEN2	Benign	0.024	T;T;T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.067
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.89	.;D;D;D
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.082	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.2	N;.;N;.
PhyloP100		5.8
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	1.2	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.53	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0010	B;.;B;.
Vest4		0.20
MutPred		0.45		Gain of phosphorylation at C14 (P = 0.0409);Gain of phosphorylation at C14 (P = 0.0409);Gain of phosphorylation at C14 (P = 0.0409);Gain of phosphorylation at C14 (P = 0.0409);
MVP		0.043
MPC		0.92
ClinPred		0.64	D
GERP RS		5.6
PromoterAI		-0.0020	Neutral
Varity_R		0.27
gMVP		0.19
Mutation Taster		=75/25	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

hg19: chr11-120916439;