11-121045800-C-A

Position:

• chr11-121045800-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001363644.2(TBCEL):​c.110C>A​(p.Thr37Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000214 in 1,451,644 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: not found (cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: TBCEL NM_001363644.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12550455).
• BS2: High AC in GnomAdExome4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCEL	NM_001363644.2	c.110C>A	p.Thr37Lys	missense_variant	3/9	ENST00000683345.1	NP_001350573.1
TBCEL-TECTA	NM_001378761.1	c.110C>A	p.Thr37Lys	missense_variant	2/30		NP_001365690.1
TBCEL	NM_001130047.3	c.110C>A	p.Thr37Lys	missense_variant	2/8		NP_001123519.1
TBCEL	NM_152715.5	c.110C>A	p.Thr37Lys	missense_variant	2/8		NP_689928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCEL	ENST00000683345.1	c.110C>A	p.Thr37Lys	missense_variant	3/9		NM_001363644.2	ENSP00000507873.1
TBCEL-TECTA	ENST00000645041.1	c.62C>A	p.Thr21Lys	missense_variant	1/10			ENSP00000496315.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000829 AC: 2 AN: 241266 Hom.: 0 AF XY: 0.00000764 AC XY: 1 AN XY: 130878

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000214 AC: 31 AN: 1451644 Hom.: 0 Cov.: 30 AF XY: 0.0000166 AC XY: 12 AN XY: 722064

Gnomad4 AFR exome AF: 0.0000305

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 02, 2023

The c.110C>A (p.T37K) alteration is located in exon 2 (coding exon 1) of the TBCEL gene. This alteration results from a C to A substitution at nucleotide position 110, causing the threonine (T) at amino acid position 37 to be replaced by a lysine (K). 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	0.26
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.013	T;T;T;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	.;D;D;D;D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.065	N;.;N;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.13	N;N;N;N;.
REVEL	Benign	0.15
Sift	Benign	0.31	T;T;T;T;.
Sift4G	Benign	0.093	T;T;T;T;.
Polyphen		0.029	B;.;B;.;.
Vest4		0.52
MutPred		0.47		Loss of phosphorylation at T37 (P = 0.008);Loss of phosphorylation at T37 (P = 0.008);Loss of phosphorylation at T37 (P = 0.008);Loss of phosphorylation at T37 (P = 0.008);.;
MVP		0.51
MPC		0.96
ClinPred		0.54	D
GERP RS		4.6
Varity_R		0.075
gMVP		0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs1461438871; hg19: chr11-120916509;