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 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 rank	MANE	Protein	UniProt
TBC1D8B	NM_017752.3	c.241+188delT		intron_variant	Intron 2 of 20	ENST00000357242.10	NP_060222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D8B	ENST00000357242.10	c.241+173delT		intron_variant	Intron 2 of 20	1	NM_017752.3	ENSP00000349781.5

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 25, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

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;