X-106802952-C-T

Position:

• chrX-106802952-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_017752.3(TBC1D8B):​c.99C>T​(p.Gly33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 1,096,132 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000064 (0 hom. 2 hem.)
• Consequence: TBC1D8B NM_017752.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0180

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 Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant X-106802952-C-T is Benign according to our data. Variant chrX-106802952-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.018 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D8B	NM_017752.3	c.99C>T	p.Gly33=	synonymous_variant	1/21	ENST00000357242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D8B	ENST00000357242.10	c.99C>T	p.Gly33=	synonymous_variant	1/21	1	NM_017752.3	P2
TBC1D8B	ENST00000310452.6	c.99C>T	p.Gly33=	synonymous_variant	1/12	1
TBC1D8B	ENST00000481617.6	c.99C>T	p.Gly33=	synonymous_variant	1/7	1
TBC1D8B	ENST00000276175.7	c.99C>T	p.Gly33=	synonymous_variant	1/21	5		A1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000639 AC: 7 AN: 1096132 Hom.: 0 Cov.: 30 AF XY: 0.00000553 AC XY: 2 AN XY: 361682

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000663

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000109

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

TBC1D8B: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1931072814; hg19: chrX-106046182;