Variant chr22-30293770-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_031937.3(TBC1D10A):c.931C>G(p.Leu311Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TBC1D10A
NM_031937.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

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:

ENSG00000248751 (HGNC:):

ENSG00000248751 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D10A	NM_031937.3 linkuse as main transcript	c.931C>G	p.Leu311Val	missense_variant	8/9	ENST00000215790.12	NP_114143.1	Q9BXI6-1A7E244B7ZVY9
TBC1D10A	NM_001204240.2 linkuse as main transcript	c.952C>G	p.Leu318Val	missense_variant	8/9		NP_001191169.1	Q9BXI6-2A7E244

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D10A	ENST00000215790.12 linkuse as main transcript	c.931C>G	p.Leu311Val	missense_variant	8/9	1	NM_031937.3	ENSP00000215790.8		Q9BXI6-1
ENSG00000248751	ENST00000434291.5 linkuse as main transcript	c.553C>G	p.Leu185Val	missense_variant	6/13	2		ENSP00000401535.1		H7C1Q1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460228

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726178

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

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

Dec 05, 2022

The c.952C>G (p.L318V) alteration is located in exon 8 (coding exon 8) of the TBC1D10A gene. This alteration results from a C to G substitution at nucleotide position 952, causing the leucine (L) at amino acid position 318 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

0.24

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.077

.;T;.;T

Eigen

Benign

0.087

Eigen_PC

Benign

0.029

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Pathogenic

0.88

D;D;D;D

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.9

.;M;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Uncertain

0.42

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.99

.;D;.;.

Vest4

0.60, 0.61, 0.59

MutPred

0.81

.;Gain of methylation at K312 (P = 0.0314);.;.;

MVP

0.048

MPC

0.40

ClinPred

0.96

GERP RS

1.1

Varity_R

0.17

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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