chrX-106818945-GT-G

Position:

• chrX-106818945-GT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_017752.3(TBC1D8B):​c.241+188del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.094 (1111 hom., 1815 hem., cov: 19)
• Consequence: TBC1D8B NM_017752.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-106818945-GT-G is Benign according to our data. Variant chrX-106818945-GT-G is described in ClinVar as [Benign]. Clinvar id is 1245948.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D8B	NM_017752.3	c.241+188del		intron_variant		ENST00000357242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D8B	ENST00000357242.10	c.241+188del		intron_variant		1	NM_017752.3	P2

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 9320 AN: 98897 Hom.: 1111 Cov.: 19 AF XY: 0.0696 AC XY: 1805 AN XY: 25943

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.00619

Gnomad EAS AF: 0.00315

Gnomad SAS AF: 0.00492

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.00930

Gnomad NFE AF: 0.00547

Gnomad OTH AF: 0.0742

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0944 AC: 9331 AN: 98887 Hom.: 1111 Cov.: 19 AF XY: 0.0699 AC XY: 1815 AN XY: 25953

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.0419

Gnomad4 ASJ AF: 0.00619

Gnomad4 EAS AF: 0.00316

Gnomad4 SAS AF: 0.00496

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.00547

Gnomad4 OTH AF: 0.0737

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs370976127; hg19: chrX-106062175;