11-121060070-A-G

Position:

• chr11-121060070-A-G

Variant summary

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

The NM_001363644.2(TBCEL):​c.941A>G​(p.Glu314Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBCEL NM_001363644.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.76

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31843528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCEL	NM_001363644.2	c.941A>G	p.Glu314Gly	missense_variant	8/9	ENST00000683345.1	NP_001350573.1
TBCEL-TECTA	NM_001378761.1	c.941A>G	p.Glu314Gly	missense_variant	7/30		NP_001365690.1
TBCEL	NM_001130047.3	c.941A>G	p.Glu314Gly	missense_variant	7/8		NP_001123519.1
TBCEL	NM_152715.5	c.941A>G	p.Glu314Gly	missense_variant	7/8		NP_689928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCEL	ENST00000683345.1	c.941A>G	p.Glu314Gly	missense_variant	8/9		NM_001363644.2	ENSP00000507873.1
TBCEL-TECTA	ENST00000645041.1	c.893A>G	p.Glu298Gly	missense_variant	6/10			ENSP00000496315.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Sep 03, 2024

The c.941A>G (p.E314G) alteration is located in exon 7 (coding exon 6) of the TBCEL gene. This alteration results from a A to G substitution at nucleotide position 941, causing the glutamic acid (E) at amino acid position 314 to be replaced by a glycine (G). 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	0.083
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T;T;.;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	.;D;T;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M;M;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.3	N;N;N;.
REVEL	Benign	0.25
Sift	Benign	0.17	T;T;T;.
Sift4G	Uncertain	0.022	D;D;D;.
Polyphen		0.88	P;P;.;.
Vest4		0.31
MutPred		0.51		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);.;.;
MVP		0.22
MPC		1.2
ClinPred		0.93	D
GERP RS		5.6
Varity_R		0.17
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-120930779;