Variant chrX-106802972-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017752.3(TBC1D8B):c.119G>A(p.Gly40Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000366 in 1,092,894 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000037 ( 0 hom. 0 hem. )

Consequence

TBC1D8B
NM_017752.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.05

Variant links:

Genes affected

TBC1D8B (HGNC:24715): (TBC1 domain family member 8B) This gene encodes a protein with a TBC (Tre-2/Bub2/CDC16) domain. Some mammalian proteins with this domain have been shown to function as Rab-GAPs by binding to specific Rab proteins and affecting their GTPase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

TBC1D8B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D8B	NM_017752.3 linkuse as main transcript	c.119G>A	p.Gly40Glu	missense_variant	1/21	ENST00000357242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D8B	ENST00000357242.10 linkuse as main transcript	c.119G>A	p.Gly40Glu	missense_variant	1/21	1	NM_017752.3	P2	Q0IIM8-1
TBC1D8B	ENST00000310452.6 linkuse as main transcript	c.119G>A	p.Gly40Glu	missense_variant	1/12	1			Q0IIM8-3
TBC1D8B	ENST00000481617.6 linkuse as main transcript	c.119G>A	p.Gly40Glu	missense_variant	1/7	1
TBC1D8B	ENST00000276175.7 linkuse as main transcript	c.119G>A	p.Gly40Glu	missense_variant	1/21	5		A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000578

AC:

AN:

172886

Hom.:

AF XY:

0.00

AC XY:

AN XY:

59362

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:

0.0000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000366

AC:

AN:

1092894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

358966

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:

0.00000476

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

TBC1D8B-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 10, 2023

The TBC1D8B c.119G>A variant is predicted to result in the amino acid substitution p.Gly40Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0013% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/X-106046202-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;.;T;T

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.71

T;T;T;T

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.44

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.7

D;D;D;D

REVEL

Benign

0.21

Sift

Benign

0.12

T;T;T;T

Sift4G

Uncertain

0.013

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.60

MutPred

0.34

Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);

MVP

0.34

MPC

0.48

ClinPred

0.89

GERP RS

5.2

Varity_R

0.71

gMVP

0.51

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