X-106820880-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2

The NM_017752.3(TBC1D8B):c.245C>A(p.Ala82Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000688 in 1,163,343 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000057 ( 0 hom. 3 hem. )

Consequence

TBC1D8B
NM_017752.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

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 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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09587476).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000018 (2/111235) while in subpopulation SAS AF = 0.000754 (2/2654). AF 95% confidence interval is 0.000134. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAdExome4 at 6 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017752.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D8B	NM_017752.3	MANE Select	c.245C>A	p.Ala82Asp	missense	Exon 3 of 21	NP_060222.2
TBC1D8B	NM_001441214.1		c.245C>A	p.Ala82Asp	missense	Exon 3 of 20	NP_001428143.1
TBC1D8B	NM_198881.2		c.245C>A	p.Ala82Asp	missense	Exon 3 of 12	NP_942582.1	Q0IIM8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D8B	ENST00000357242.10	TSL:1 MANE Select	c.245C>A	p.Ala82Asp	missense	Exon 3 of 21	ENSP00000349781.5	Q0IIM8-1
TBC1D8B	ENST00000310452.6	TSL:1	c.245C>A	p.Ala82Asp	missense	Exon 3 of 12	ENSP00000310675.2	Q0IIM8-3
TBC1D8B	ENST00000481617.6	TSL:1	c.245C>A	p.Ala82Asp	missense	Exon 3 of 7	ENSP00000421375.1	D6RFZ2

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111183

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:

0.000751

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

158912

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000570

AC:

AN:

1052108

Hom.:

Cov.:

AF XY:

0.00000908

AC XY:

AN XY:

330218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24620

American (AMR)

AF:

0.00

AC:

AN:

30783

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18715

East Asian (EAS)

AF:

0.00

AC:

AN:

28787

South Asian (SAS)

AF:

0.000126

AC:

AN:

47703

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40289

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3850

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

813033

Other (OTH)

AF:

0.00

AC:

AN:

44328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111235

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33653

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30714

American (AMR)

AF:

0.00

AC:

AN:

10451

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2629

East Asian (EAS)

AF:

0.00

AC:

AN:

3557

South Asian (SAS)

AF:

0.000754

AC:

AN:

2654

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6015

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52804

Other (OTH)

AF:

0.00

AC:

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nephrotic syndrome, type 20 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.082

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.68

M_CAP

Benign

0.048

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

4.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.2

REVEL

Benign

0.17

Sift

Benign

0.050

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.23

MutPred

0.36

Gain of solvent accessibility (P = 0.0202)

MVP

0.26

MPC

0.34

ClinPred

0.72

GERP RS

5.1

Varity_R

0.61

gMVP

0.66

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over