NM_017752.3:c.119G>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G40V) has been classified 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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

nephrotic syndrome, type 20
Inheritance: XL Classification: STRONG, MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TBC1D8B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D8B	NM_017752.3 link	c.119G>A	p.Gly40Glu	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>A	p.Gly40Glu	missense_variant	Exon 1 of 21	1	NM_017752.3	ENSP00000349781.5	Q0IIM8-1
TBC1D8B	ENST00000310452.6 link	c.119G>A	p.Gly40Glu	missense_variant	Exon 1 of 12	1		ENSP00000310675.2	Q0IIM8-3
TBC1D8B	ENST00000481617.6 link	c.119G>A	p.Gly40Glu	missense_variant	Exon 1 of 7	1		ENSP00000421375.1	D6RFZ2
TBC1D8B	ENST00000276175.7 link	c.119G>A	p.Gly40Glu	missense_variant	Exon 1 of 21	5		ENSP00000276175.3	J3KN75

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000578

AC:

AN:

172886

AF XY:

0.00

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 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

African (AFR)

AF:

0.00

AC:

AN:

26360

American (AMR)

AF:

0.00

AC:

AN:

34957

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19117

East Asian (EAS)

AF:

0.00

AC:

AN:

30134

South Asian (SAS)

AF:

0.00

AC:

AN:

53053

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3984

European-Non Finnish (NFE)

AF:

0.00000476

AC:

AN:

840109

Other (OTH)

AF:

0.00

AC:

AN:

45892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Apr 10, 2023

PreventionGenetics, part of Exact Sciences

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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;.;.

PhyloP100

9.1

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

PromoterAI

-0.010

Neutral

(source)

Varity_R

0.71

gMVP

0.51

Mutation Taster

=67/33

polymorphism

(source)

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

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NM_017752.3:c.119G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over