X-106818722-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 5P and 4B. PP3_StrongPP5BS2

The NM_017752.3(TBC1D8B):c.190C>T(p.Arg64Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000034 in 1,206,577 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R64H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000036 ( 0 hom. 12 hem. )

Consequence

TBC1D8B
NM_017752.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.51

Publications

2 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 links:

MORC4 (HGNC:23485): (MORC family CW-type zinc finger 4) In human, the four current members of the microrchidia (morc) gene family share an N-terminal ATPase-like ATP-binding region and a CW four-cysteine zinc-finger motif. The protein encoded by this gene also has a nuclear matrix binding domain and a two-stranded coiled-coil motif near its C-terminus. This gene is widely expressed at low levels in normal tissues and has elevated expression in placenta and testis. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

MORC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.94

PP5

Variant X-106818722-C-T is Pathogenic according to our data. Variant chrX-106818722-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1013502.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAdExome4 at 39 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D8B	NM_017752.3 link	c.190C>T	p.Arg64Cys	missense_variant	Exon 2 of 21	ENST00000357242.10	NP_060222.2	Q0IIM8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D8B	ENST00000357242.10 link	c.190C>T	p.Arg64Cys	missense_variant	Exon 2 of 21	1	NM_017752.3	ENSP00000349781.5		Q0IIM8-1

Frequencies

GnomAD3 genomes

AF:

0.0000181

AC:

AN:

110743

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000379

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000110

AC:

AN:

181472

AF XY:

0.0000151

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:

0.0000247

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1095834

Hom.:

Cov.:

AF XY:

0.0000332

AC XY:

AN XY:

361936

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26315

American (AMR)

AF:

0.00

AC:

AN:

35116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19306

East Asian (EAS)

AF:

0.00

AC:

AN:

30140

South Asian (SAS)

AF:

0.00

AC:

AN:

53905

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4125

European-Non Finnish (NFE)

AF:

0.0000428

AC:

AN:

840571

Other (OTH)

AF:

0.0000653

AC:

AN:

45968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000181

AC:

AN:

110743

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33093

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30573

American (AMR)

AF:

0.00

AC:

AN:

10339

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2629

East Asian (EAS)

AF:

0.00

AC:

AN:

3531

South Asian (SAS)

AF:

0.00

AC:

AN:

2625

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5915

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000379

AC:

AN:

52720

Other (OTH)

AF:

0.00

AC:

AN:

1490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Nephrotic syndrome, type 20

Pathogenic:1

Aug 30, 2023

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

T;.;T;T

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Pathogenic

0.84

MetaRNN

Pathogenic

0.94

D;D;D;D

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.7

M;M;.;.

PhyloP100

4.5

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-6.0

D;D;D;D

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.91

MutPred

0.75

Gain of methylation at K59 (P = 0.0395);Gain of methylation at K59 (P = 0.0395);Gain of methylation at K59 (P = 0.0395);Gain of methylation at K59 (P = 0.0395);

MVP

0.48

MPC

0.52

ClinPred

0.98

GERP RS

5.8

PromoterAI

-0.0059

Neutral

(source)

Varity_R

0.81

gMVP

0.89

Mutation Taster

=56/44

disease causing (ClinVar)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

X-106818722-C-T

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