NM_017752.3:c.241+188dupT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_017752.3(TBC1D8B):​c.241+188dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0035 (0 hom., 16 hem., cov: 19)
• Consequence: TBC1D8B NM_017752.3 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0035 (346/98879) while in subpopulation EAS AF= 0.00664 (21/3163). AF 95% confidence interval is 0.00445. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 16 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D8B	NM_017752.3	c.241+188dupT		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+172_241+173insT		intron_variant	Intron 2 of 20	1	NM_017752.3	ENSP00000349781.5

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 347 AN: 98890 Hom.: 0 Cov.: 19 AF XY: 0.000617 AC XY: 16 AN XY: 25924

Gnomad AFR AF: 0.00114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00298

Gnomad ASJ AF: 0.00248

Gnomad EAS AF: 0.00662

Gnomad SAS AF: 0.000894

Gnomad FIN AF: 0.0301

Gnomad MID AF: 0.00930

Gnomad NFE AF: 0.00263

Gnomad OTH AF: 0.00154

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

GnomAD4 genome AF: 0.00350 AC: 346 AN: 98879 Hom.: 0 Cov.: 19 AF XY: 0.000617 AC XY: 16 AN XY: 25933

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.00298

Gnomad4 ASJ AF: 0.00248

Gnomad4 EAS AF: 0.00664

Gnomad4 SAS AF: 0.000900

Gnomad4 FIN AF: 0.0301

Gnomad4 NFE AF: 0.00263

Gnomad4 OTH AF: 0.00153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;