Variant chr22-30292670-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000215790.12(TBC1D10A):c.1232G>A(p.Arg411His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,608,414 control chromosomes in the GnomAD database, including 11,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.088 ( 782 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10366 hom. )

Consequence

TBC1D10A
ENST00000215790.12 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.35

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014603138).

BP6

Variant 22-30292670-C-T is Benign according to our data. Variant chr22-30292670-C-T is described in ClinVar as [Benign]. Clinvar id is 1226011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D10A	NM_031937.3 linkuse as main transcript	c.1232G>A	p.Arg411His	missense_variant	9/9	ENST00000215790.12	NP_114143.1
TBC1D10A	NM_001204240.2 linkuse as main transcript	c.1253G>A	p.Arg418His	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.1232G>A	p.Arg411His	missense_variant	9/9	1	NM_031937.3	ENSP00000215790	P1	Q9BXI6-1

Frequencies

GnomAD3 genomes

AF:

0.0879

AC:

13344

AN:

151780

Hom.:

781

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0256

Gnomad FIN

AF:

0.0894

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.0917

AC:

22537

AN:

245752

Hom.:

1322

AF XY:

0.0933

AC XY:

12382

AN XY:

132776

show subpopulations

Gnomad AFR exome

AF:

0.0209

Gnomad AMR exome

AF:

0.0756

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0341

Gnomad FIN exome

AF:

0.0933

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.113

AC:

164491

AN:

1456516

Hom.:

10366

Cov.:

AF XY:

0.111

AC XY:

80723

AN XY:

724002

show subpopulations

Gnomad4 AFR exome

AF:

0.0182

Gnomad4 AMR exome

AF:

0.0792

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0347

Gnomad4 FIN exome

AF:

0.0866

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.0879

AC:

13345

AN:

151898

Hom.:

782

Cov.:

AF XY:

0.0844

AC XY:

6267

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.0238

Gnomad4 AMR

AF:

0.103

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0258

Gnomad4 FIN

AF:

0.0894

Gnomad4 NFE

AF:

0.130

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.128

Hom.:

2600

Bravo

AF:

0.0882

TwinsUK

AF:

0.125

AC:

463

ALSPAC

AF:

0.131

AC:

505

ESP6500AA

AF:

0.0261

AC:

115

ESP6500EA

AF:

0.137

AC:

1176

ExAC

AF:

0.0898

AC:

10903

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2019	This variant is associated with the following publications: (PMID: 30389748) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.88

D;D;D

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

0.92

P;P;P

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.70

N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.011

D;D;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.99

D;.;.

Vest4

0.048

MPC

0.42

ClinPred

0.014

GERP RS

5.5

Varity_R

0.073

gMVP

0.30

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