X-106802972-G-C

Variant names:

• chrX-106802972-G-C
• rs754093308
• NM_017752.3:c.119G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017752.3(TBC1D8B):​c.119G>C​(p.Gly40Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,092,894 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: TBC1D8B NM_017752.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.05

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25771263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D8B	NM_017752.3	c.119G>C	p.Gly40Ala	missense_variant	Exon 1 of 21	ENST00000357242.10	NP_060222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D8B	ENST00000357242.10	c.119G>C	p.Gly40Ala	missense_variant	Exon 1 of 21	1	NM_017752.3	ENSP00000349781.5
TBC1D8B	ENST00000310452.6	c.119G>C	p.Gly40Ala	missense_variant	Exon 1 of 12	1		ENSP00000310675.2
TBC1D8B	ENST00000481617.6	c.119G>C	p.Gly40Ala	missense_variant	Exon 1 of 7	1		ENSP00000421375.1
TBC1D8B	ENST00000276175.7	c.119G>C	p.Gly40Ala	missense_variant	Exon 1 of 21	5		ENSP00000276175.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000578 AC: 1 AN: 172886 Hom.: 0 AF XY: 0.0000168 AC XY: 1 AN XY: 59362

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 SAS exome AF: 0.0000579

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 3 AN: 1092894 Hom.: 0 Cov.: 30 AF XY: 0.00000279 AC XY: 1 AN XY: 358966

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: 0.0000565

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T;.;T;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.2	N;D;D;N
REVEL	Benign	0.15
Sift	Benign	0.14	T;T;T;T
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		1.0	D;.;P;.
Vest4		0.48
MutPred		0.38		Loss of disorder (P = 0.0666);Loss of disorder (P = 0.0666);Loss of disorder (P = 0.0666);Loss of disorder (P = 0.0666);
MVP		0.43
MPC		0.17
ClinPred		0.62	D
GERP RS		5.2
Varity_R		0.46
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs754093308; hg19: chrX-106046202;