X-106818945-GTT-GTTT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_017752.3(TBC1D8B):​c.241+188dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 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
• 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: Uncertain_significance. The variant received 0 ACMG points.

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

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00113 AC: 31 AN: 27340

American (AMR) AF: 0.00298 AC: 27 AN: 9059

Ashkenazi Jewish (ASJ) AF: 0.00248 AC: 6 AN: 2423

East Asian (EAS) AF: 0.00664 AC: 21 AN: 3163

South Asian (SAS) AF: 0.000900 AC: 2 AN: 2221

European-Finnish (FIN) AF: 0.0301 AC: 129 AN: 4281

Middle Eastern (MID) AF: 0.00515 AC: 1 AN: 194

European-Non Finnish (NFE) AF: 0.00263 AC: 127 AN: 48269

Other (OTH) AF: 0.00153 AC: 2 AN: 1310

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000672 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Other links and lift over

dbSNP: rs370976127; hg19: chrX-106062175; COSMIC: COSV52175409;