Variant chr11-67404237-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000542590.2(TBC1D10C):c.35C>T(p.Pro12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,433,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

TBC1D10C
ENST00000542590.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93

Variant links:

Genes affected

TBC1D10C (HGNC:24702): (TBC1 domain family member 10C) The protein encoded by this gene has an N-terminal Rab-GTPase domain and a binding site at the C-terminus for calcineurin, and is an inhibitor of both the Ras signaling pathway and calcineurin, a phosphatase regulated by calcium and calmodulin. Genes encoding similar proteins are located on chromosomes 16 and 22. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2013]

TBC1D10C links:

TBC1D10C (HGNC:):

TBC1D10C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11006716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D10C	NM_001369496.1 linkuse as main transcript	c.35C>T	p.Pro12Leu	missense_variant	1/9	ENST00000542590.2	NP_001356425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D10C	ENST00000542590.2 linkuse as main transcript	c.35C>T	p.Pro12Leu	missense_variant	1/9	1	NM_001369496.1	ENSP00000443654.1		Q8IV04-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1433276

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.35C>T (p.P12L) alteration is located in exon 2 (coding exon 1) of the TBC1D10C gene. This alteration results from a C to T substitution at nucleotide position 35, causing the proline (P) at amino acid position 12 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

Benign

0.072

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.036

.;.;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.78

.;T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.99

N;N;N

REVEL

Benign

0.099

Sift

Uncertain

0.0020

D;T;T

Sift4G

Uncertain

0.025

D;D;T

Polyphen

0.0

.;.;B

Vest4

0.18

MutPred

0.26

Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);

MVP

0.51

MPC

0.21

ClinPred

0.24

GERP RS

4.3

Varity_R

0.069

gMVP

0.44

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over