NM_001363644.2:c.595T>C

Variant names:

• chr11-121055191-T-C
• NM_001363644.2:c.595T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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 2 ACMG points.

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

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.595T>C	p.Phe199Leu	missense	Exon 6 of 9	NP_001350573.1	Q5QJ74
	TBCEL-TECTA	NM_001378761.1		c.595T>C	p.Phe199Leu	missense	Exon 5 of 30	NP_001365690.1
	TBCEL	NM_001130047.3		c.595T>C	p.Phe199Leu	missense	Exon 5 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.595T>C	p.Phe199Leu	missense	Exon 6 of 9	ENSP00000507873.1	Q5QJ74
	TBCEL-TECTA	ENST00000645041.1		c.547T>C	p.Phe183Leu	missense	Exon 4 of 10	ENSP00000496315.1	A0A2R8YFB7
	TBCEL	ENST00000422003.6	TSL:1	c.595T>C	p.Phe199Leu	missense	Exon 5 of 8	ENSP00000403925.2	Q5QJ74

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	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
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0058	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		8.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.24
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.018	D
Polyphen		0.93	P
Vest4		0.56
MutPred		0.41		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
Mutation Taster		=22/78	disease causing

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: chr11-120925900;