Genetic Variant TBC1D8B:p.Gly40Val (chrX-106802972-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_017752.3(TBC1D8B):c.119G>T(p.Gly40Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000034 in 1,204,856 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000033 ( 0 hom. 12 hem. )

Consequence

TBC1D8B
NM_017752.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21612483).

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000447 (5/111962) while in subpopulation AMR AF= 0.000471 (5/10619). AF 95% confidence interval is 0.000185. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAdExome4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D8B	NM_017752.3 link	c.119G>T	p.Gly40Val	missense_variant	Exon 1 of 21	ENST00000357242.10	NP_060222.2	Q0IIM8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBC1D8B	ENST00000357242.10 link	c.119G>T	p.Gly40Val	missense_variant	Exon 1 of 21	1	NM_017752.3	ENSP00000349781.5	Q0IIM8-1
TBC1D8B	ENST00000310452.6 link	c.119G>T	p.Gly40Val	missense_variant	Exon 1 of 12	1		ENSP00000310675.2	Q0IIM8-3
TBC1D8B	ENST00000481617.6 link	c.119G>T	p.Gly40Val	missense_variant	Exon 1 of 7	1		ENSP00000421375.1	D6RFZ2
TBC1D8B	ENST00000276175.7 link	c.119G>T	p.Gly40Val	missense_variant	Exon 1 of 21	5		ENSP00000276175.3	J3KN75

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

111962

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34100

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000471

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000185

AC:

AN:

172886

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

59362

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00101

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:

0.00

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1092894

Hom.:

Cov.:

AF XY:

0.0000334

AC XY:

AN XY:

358966

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000915

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:

0.00000119

Gnomad4 OTH exome

AF:

0.0000654

GnomAD4 genome

AF:

0.0000447

AC:

AN:

111962

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34100

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000471

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

ExAC

AF:

0.000115

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;.;T;T

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.029

D;T;D;D

Sift4G

Uncertain

0.019

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.65

MutPred

0.43

Loss of disorder (P = 0.0198);Loss of disorder (P = 0.0198);Loss of disorder (P = 0.0198);Loss of disorder (P = 0.0198);

MVP

0.42

MPC

0.47

ClinPred

0.18

GERP RS

5.2

Varity_R

0.72

gMVP

0.50

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over