11-121055191-T-C

Position:

• chr11-121055191-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001363644.2(TBCEL):​c.595T>C​(p.Phe199Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 8.01

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCEL	NM_001363644.2	c.595T>C	p.Phe199Leu	missense_variant	6/9	ENST00000683345.1	NP_001350573.1
TBCEL-TECTA	NM_001378761.1	c.595T>C	p.Phe199Leu	missense_variant	5/30		NP_001365690.1
TBCEL	NM_001130047.3	c.595T>C	p.Phe199Leu	missense_variant	5/8		NP_001123519.1
TBCEL	NM_152715.5	c.595T>C	p.Phe199Leu	missense_variant	5/8		NP_689928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCEL	ENST00000683345.1	c.595T>C	p.Phe199Leu	missense_variant	6/9		NM_001363644.2	ENSP00000507873.1
TBCEL-TECTA	ENST00000645041.1	c.547T>C	p.Phe183Leu	missense_variant	4/10			ENSP00000496315.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Feb 27, 2024

The c.595T>C (p.F199L) alteration is located in exon 5 (coding exon 4) of the TBCEL gene. This alteration results from a T to C substitution at nucleotide position 595, causing the phenylalanine (F) at amino acid position 199 to be replaced by a leucine (L). 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	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;T;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	.;D;D;D
M_CAP	Benign	0.0058	T
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.1	D;D;D;.
REVEL	Benign	0.24
Sift	Uncertain	0.022	D;D;D;.
Sift4G	Uncertain	0.018	D;D;D;.
Polyphen		0.93	P;P;.;.
Vest4		0.56
MutPred		0.41		Gain of ubiquitination at K194 (P = 0.0985);Gain of ubiquitination at K194 (P = 0.0985);Gain of ubiquitination at K194 (P = 0.0985);.;
MVP		0.37
MPC		1.5
ClinPred		0.98	D
GERP RS		6.0
Varity_R		0.63
gMVP		0.76

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: chr11-120925900;