11-121055285-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_001363644.2(TBCEL):c.689G>A(p.Arg230Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,457,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TBCEL NM_001363644.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.81

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, TBCEL
• BP4: Computational evidence support a benign effect (MetaRNN=0.37064528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBCEL	NM_001363644.2	c.689G>A	p.Arg230Gln	missense_variant	6/9	ENST00000683345.1
TBCEL-TECTA	NM_001378761.1	c.689G>A	p.Arg230Gln	missense_variant	5/30
TBCEL	NM_001130047.3	c.689G>A	p.Arg230Gln	missense_variant	5/8
TBCEL	NM_152715.5	c.689G>A	p.Arg230Gln	missense_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCEL	ENST00000683345.1	c.689G>A	p.Arg230Gln	missense_variant	6/9		NM_001363644.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 247932 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134008

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000296

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457710 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724996

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.0000769

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Nov 07, 2023

The c.689G>A (p.R230Q) alteration is located in exon 5 (coding exon 4) of the TBCEL gene. This alteration results from a G to A substitution at nucleotide position 689, causing the arginine (R) at amino acid position 230 to be replaced by a glutamine (Q). 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	0.11
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Uncertain	-0.020
Cadd	Uncertain	25
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.046	T;T;T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L;L;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N;N;N;.
REVEL	Benign	0.22
Sift	Benign	0.097	T;T;T;.
Sift4G	Uncertain	0.017	D;D;D;.
Polyphen		0.79	P;P;.;.
Vest4		0.43
MutPred		0.39		Loss of phosphorylation at S233 (P = 0.0613);Loss of phosphorylation at S233 (P = 0.0613);Loss of phosphorylation at S233 (P = 0.0613);.;
MVP		0.71
MPC		1.9
ClinPred		0.57	D
GERP RS		5.6
Varity_R		0.21
gMVP		0.63

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: rs1457306216; hg19: chr11-120925994;