X-106818945-GTT-GT

Variant names:

• chrX-106818945-GT-G
• rs370976127
• NM_017752.3:c.241+188delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_017752.3(TBC1D8B):​c.241+188delT 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
• 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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017752.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D8B	NM_017752.3	MANE Select	c.241+188delT		intron	N/A	NP_060222.2
	TBC1D8B	NM_001441214.1		c.241+188delT		intron	N/A	NP_001428143.1
	TBC1D8B	NM_001441215.1		c.-54+188delT		intron	N/A	NP_001428144.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D8B	ENST00000357242.10	TSL:1 MANE Select	c.241+173delT		intron	N/A	ENSP00000349781.5	Q0IIM8-1
	TBC1D8B	ENST00000310452.6	TSL:1	c.241+173delT		intron	N/A	ENSP00000310675.2	Q0IIM8-3
	TBC1D8B	ENST00000481617.6	TSL:1	c.241+173delT		intron	N/A	ENSP00000421375.1	D6RFZ2

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 9320 AN: 98897 Hom.: 1111 Cov.: 19

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

African (AFR) AF: 0.311 AC: 8507 AN: 27332

American (AMR) AF: 0.0419 AC: 379 AN: 9056

Ashkenazi Jewish (ASJ) AF: 0.00619 AC: 15 AN: 2422

East Asian (EAS) AF: 0.00316 AC: 10 AN: 3163

South Asian (SAS) AF: 0.00496 AC: 11 AN: 2219

European-Finnish (FIN) AF: 0.0104 AC: 45 AN: 4317

Middle Eastern (MID) AF: 0.0155 AC: 3 AN: 194

European-Non Finnish (NFE) AF: 0.00547 AC: 264 AN: 48249

Other (OTH) AF: 0.0737 AC: 97 AN: 1316

Alfa AF: 0.000538 Hom.: 2

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs370976127; hg19: chrX-106062175; COSMIC: COSV52181604;