Genetic Variant NM_001363644.2:c.382G>T (chr11-121053659-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BS2

The NM_001363644.2(TBCEL):c.382G>T(p.Val128Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,452 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V128I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TBCEL
NM_001363644.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.34

Publications

0 publications found

Variant links:

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 links:

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]

TBCEL-TECTA links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCEL	NM_001363644.2 link	c.382G>T	p.Val128Phe	missense_variant	Exon 5 of 9	ENST00000683345.1	NP_001350573.1
TBCEL-TECTA	NM_001378761.1 link	c.382G>T	p.Val128Phe	missense_variant	Exon 4 of 30		NP_001365690.1
TBCEL	NM_001130047.3 link	c.382G>T	p.Val128Phe	missense_variant	Exon 4 of 8		NP_001123519.1	Q5QJ74
TBCEL	NM_152715.5 link	c.382G>T	p.Val128Phe	missense_variant	Exon 4 of 8		NP_689928.3	Q5QJ74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCEL	ENST00000683345.1 link	c.382G>T	p.Val128Phe	missense_variant	Exon 5 of 9		NM_001363644.2	ENSP00000507873.1		Q5QJ74
TBCEL-TECTA	ENST00000645041.1 link	c.334G>T	p.Val112Phe	missense_variant	Exon 3 of 10			ENSP00000496315.1		A0A2R8YFB7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460452

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726534

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33386

American (AMR)

AF:

0.00

AC:

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111120

Other (OTH)

AF:

0.0000166

AC:

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;T;T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

.;D;D;D

M_CAP

Benign

0.0080

MetaRNN

Uncertain

0.45

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;.;.

PhyloP100

4.3

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.6

N;N;N;.

REVEL

Benign

0.21

Sift

Uncertain

0.010

D;D;D;.

Sift4G

Uncertain

0.026

D;D;D;.

Polyphen

0.90

P;P;.;.

Vest4

0.86

MutPred

0.55

Loss of MoRF binding (P = 0.1069);Loss of MoRF binding (P = 0.1069);Loss of MoRF binding (P = 0.1069);.;

MVP

0.45

MPC

1.4

ClinPred

0.80

GERP RS

6.0

Varity_R

0.18

gMVP

0.84

Mutation Taster

=47/53

disease causing

(source)

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

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NM_001363644.2:c.382G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over