chr11-121045812-C-T

Variant names:

• chr11-121045812-C-T
• rs1028764515
• NM_001363644.2:c.122C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_001363644.2(TBCEL):​c.122C>T​(p.Ser41Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,438,132 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S41C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TBCEL NM_001363644.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79
• 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 4 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity TBCEL_HUMAN
• 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.122C>T	p.Ser41Phe	missense	Exon 3 of 9	NP_001350573.1	Q5QJ74
	TBCEL-TECTA	NM_001378761.1		c.122C>T	p.Ser41Phe	missense	Exon 2 of 30	NP_001365690.1
	TBCEL	NM_001130047.3		c.122C>T	p.Ser41Phe	missense	Exon 2 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.122C>T	p.Ser41Phe	missense	Exon 3 of 9	ENSP00000507873.1	Q5QJ74
	TBCEL-TECTA	ENST00000645041.1		c.74C>T	p.Ser25Phe	missense	Exon 1 of 10	ENSP00000496315.1	A0A2R8YFB7
	TBCEL	ENST00000422003.6	TSL:1	c.122C>T	p.Ser41Phe	missense	Exon 2 of 8	ENSP00000403925.2	Q5QJ74

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000439 AC: 1 AN: 228022 AF XY: 0.00

Gnomad AFR exome AF: 0.0000662

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438132 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 715010

African (AFR) AF: 0.0000314 AC: 1 AN: 31854

American (AMR) AF: 0.00 AC: 0 AN: 38154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24904

East Asian (EAS) AF: 0.00 AC: 0 AN: 39282

South Asian (SAS) AF: 0.00 AC: 0 AN: 81184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104912

Other (OTH) AF: 0.00 AC: 0 AN: 59262

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.71
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.8
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.72
MutPred		0.53		Loss of disorder (P = 0.0096)
MVP		0.49
MPC		1.9
ClinPred		0.96	D
GERP RS		5.6
PromoterAI		-0.016	Neutral
Varity_R		0.52
gMVP		0.72
Mutation Taster		=36/64	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: rs1028764515; hg19: chr11-120916521;