NM_001363644.2:c.757A>C

Variant names:

• chr11-121058389-A-C
• NM_001363644.2:c.757A>C

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.757A>C​(p.Lys253Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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: 7.27
• 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=0.2625512).

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.757A>C	p.Lys253Gln	missense	Exon 7 of 9	NP_001350573.1	Q5QJ74
	TBCEL-TECTA	NM_001378761.1		c.757A>C	p.Lys253Gln	missense	Exon 6 of 30	NP_001365690.1
	TBCEL	NM_001130047.3		c.757A>C	p.Lys253Gln	missense	Exon 6 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.757A>C	p.Lys253Gln	missense	Exon 7 of 9	ENSP00000507873.1	Q5QJ74
	TBCEL-TECTA	ENST00000645041.1		c.709A>C	p.Lys237Gln	missense	Exon 5 of 10	ENSP00000496315.1	A0A2R8YFB7
	TBCEL	ENST00000422003.6	TSL:1	c.757A>C	p.Lys253Gln	missense	Exon 6 of 8	ENSP00000403925.2	Q5QJ74

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.11
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	0.065
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.12
Sift	Benign	0.51	T
Sift4G	Uncertain	0.025	D
Polyphen		0.013	B
Vest4		0.39
MutPred		0.35		Loss of ubiquitination at K253 (P = 0.0148)
MVP		0.30
MPC		1.3
ClinPred		0.66	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.63
Mutation Taster		=81/19	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: chr11-120929098;