X-106802873-A-G

Position:

• chrX-106802873-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_017752.3(TBC1D8B):​c.20A>G​(p.Glu7Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,097,831 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 (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000055 (0 hom. 0 hem.)
• Consequence: TBC1D8B NM_017752.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.61

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D8B	NM_017752.3	c.20A>G	p.Glu7Gly	missense_variant	1/21	ENST00000357242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D8B	ENST00000357242.10	c.20A>G	p.Glu7Gly	missense_variant	1/21	1	NM_017752.3	P2
TBC1D8B	ENST00000310452.6	c.20A>G	p.Glu7Gly	missense_variant	1/12	1
TBC1D8B	ENST00000481617.6	c.20A>G	p.Glu7Gly	missense_variant	1/7	1
TBC1D8B	ENST00000276175.7	c.20A>G	p.Glu7Gly	missense_variant	1/21	5		A1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000547 AC: 6 AN: 1097831 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 363213

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000713

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nephrotic syndrome, type 20 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

MVZ Medizinische Genetik Mainz

Sep 24, 2021

ACMG Criteria: PM2_SUP, PP3 (ACMG Version 3) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T;.;T;T
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.65	D;D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.6	M;M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-4.3	D;D;D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;.;P;.
Vest4		0.71
MutPred		0.39		Gain of MoRF binding (P = 0.0342);Gain of MoRF binding (P = 0.0342);Gain of MoRF binding (P = 0.0342);Gain of MoRF binding (P = 0.0342);
MVP		0.28
MPC		0.48
ClinPred		1.0	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.71
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-106046103;