NM_001363644.2:c.74G>C

Variant names:

• chr11-121045764-G-C
• rs138695287
• NM_001363644.2:c.74G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001363644.2(TBCEL):​c.74G>C​(p.Arg25Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R25H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBCEL NM_001363644.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.54
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4153546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCEL	NM_001363644.2	c.74G>C	p.Arg25Pro	missense_variant	Exon 3 of 9	ENST00000683345.1	NP_001350573.1
TBCEL-TECTA	NM_001378761.1	c.74G>C	p.Arg25Pro	missense_variant	Exon 2 of 30		NP_001365690.1
TBCEL	NM_001130047.3	c.74G>C	p.Arg25Pro	missense_variant	Exon 2 of 8		NP_001123519.1
TBCEL	NM_152715.5	c.74G>C	p.Arg25Pro	missense_variant	Exon 2 of 8		NP_689928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCEL	ENST00000683345.1	c.74G>C	p.Arg25Pro	missense_variant	Exon 3 of 9		NM_001363644.2	ENSP00000507873.1
TBCEL-TECTA	ENST00000645041.1	c.26G>C	p.Arg9Pro	missense_variant	Exon 1 of 10			ENSP00000496315.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248748 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T;T;T;T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.42	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;L;.;.
PhyloP100		9.5
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.25	N;N;N;N;.
REVEL	Uncertain	0.32
Sift	Benign	0.27	T;T;T;T;.
Sift4G	Benign	0.14	T;T;T;T;.
Polyphen		0.99	D;.;D;.;.
Vest4		0.67
MutPred		0.33		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;
MVP		0.56
MPC		2.1
ClinPred		0.86	D
GERP RS		4.7
PromoterAI		-0.051	Neutral
Varity_R		0.29
gMVP		0.78
Mutation Taster		=49/51	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

dbSNP: rs138695287; hg19: chr11-120916473;