chrX-106822085-G-C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_017752.3(TBC1D8B):c.469G>C(p.Glu157Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,208,721 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.000022 ( 0 hom. 8 hem. )
Consequence
TBC1D8B
NM_017752.3 missense
NM_017752.3 missense
Scores
10
6
1
Clinical Significance
Conservation
PhyloP100: 9.96
Publications
0 publications found
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]
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.971
BS2
High AC in GnomAdExome4 at 24 XL,AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000897 AC: 1AN: 111529Hom.: 0 Cov.: 22 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
111529
Hom.:
Cov.:
22
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000109 AC: 2AN: 182883 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
182883
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000219 AC: 24AN: 1097192Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 8AN XY: 362960 show subpopulations
GnomAD4 exome
AF:
AC:
24
AN:
1097192
Hom.:
Cov.:
30
AF XY:
AC XY:
8
AN XY:
362960
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26346
American (AMR)
AF:
AC:
0
AN:
35117
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19348
East Asian (EAS)
AF:
AC:
0
AN:
30183
South Asian (SAS)
AF:
AC:
0
AN:
54077
European-Finnish (FIN)
AF:
AC:
0
AN:
40490
Middle Eastern (MID)
AF:
AC:
0
AN:
4128
European-Non Finnish (NFE)
AF:
AC:
24
AN:
841452
Other (OTH)
AF:
AC:
0
AN:
46051
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000897 AC: 1AN: 111529Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33773 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
111529
Hom.:
Cov.:
22
AF XY:
AC XY:
0
AN XY:
33773
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30734
American (AMR)
AF:
AC:
0
AN:
10455
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2641
East Asian (EAS)
AF:
AC:
0
AN:
3534
South Asian (SAS)
AF:
AC:
0
AN:
2660
European-Finnish (FIN)
AF:
AC:
0
AN:
6049
Middle Eastern (MID)
AF:
AC:
0
AN:
238
European-Non Finnish (NFE)
AF:
AC:
1
AN:
53035
Other (OTH)
AF:
AC:
0
AN:
1499
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Feb 13, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.469G>C (p.E157Q) alteration is located in exon 4 (coding exon 4) of the TBC1D8B gene. This alteration results from a G to C substitution at nucleotide position 469, causing the glutamic acid (E) at amino acid position 157 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;D;D
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;.;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;D;D;N
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;T;D
Polyphen
B;.;P;.
Vest4
MutPred
Loss of ubiquitination at K156 (P = 0.0304);Loss of ubiquitination at K156 (P = 0.0304);Loss of ubiquitination at K156 (P = 0.0304);Loss of ubiquitination at K156 (P = 0.0304);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 4
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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