Variant 22-30292634-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000215790.12(TBC1D10A):c.1268C>T(p.Ala423Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

TBC1D10A
ENST00000215790.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.107

Variant links:

Genes affected

TBC1D10A (HGNC:23609): (TBC1 domain family member 10A) Enables PDZ domain binding activity. Involved in activation of cysteine-type endopeptidase activity and retrograde transport, endosome to Golgi. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D10A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054713637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D10A	NM_031937.3 linkuse as main transcript	c.1268C>T	p.Ala423Val	missense_variant	9/9	ENST00000215790.12	NP_114143.1
TBC1D10A	NM_001204240.2 linkuse as main transcript	c.1289C>T	p.Ala430Val	missense_variant	9/9		NP_001191169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D10A	ENST00000215790.12 linkuse as main transcript	c.1268C>T	p.Ala423Val	missense_variant	9/9	1	NM_031937.3	ENSP00000215790	P1	Q9BXI6-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249696

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134918

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460606

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726500

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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 04, 2022

The c.1289C>T (p.A430V) alteration is located in exon 9 (coding exon 9) of the TBC1D10A gene. This alteration results from a C to T substitution at nucleotide position 1289, causing the alanine (A) at amino acid position 430 to be replaced by a valine (V). 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

0.070

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0088

T;.;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.52

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.055

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

L;.;.

MutationTaster

Benign

0.91

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.50

N;N;N

REVEL

Benign

0.058

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.42

T;T;T

Polyphen

0.047

B;.;.

Vest4

0.067

MutPred

0.18

Loss of relative solvent accessibility (P = 0.0186);.;.;

MVP

0.25

MPC

0.13

ClinPred

0.14

GERP RS

4.5

Varity_R

0.030

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over