X-106818945-GTT-GTTTT

Variant names:

• chrX-106818945-G-GTT
• rs370976127
• NM_017752.3:c.241+187_241+188dupTT

Variant summary

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

The NM_017752.3(TBC1D8B):​c.241+187_241+188dupTT 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 0.000061 (0 hom., 0 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+187_241+188dupTT		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+173insTT		intron_variant	Intron 2 of 20	1	NM_017752.3	ENSP00000349781.5

Frequencies

GnomAD3 genomes AF: 0.0000606 AC: 6 AN: 98994 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000207

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000606 AC: 6 AN: 98984 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 26010

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

African (AFR) AF: 0.00 AC: 0 AN: 27355

American (AMR) AF: 0.00 AC: 0 AN: 9068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2423

East Asian (EAS) AF: 0.00 AC: 0 AN: 3165

South Asian (SAS) AF: 0.00 AC: 0 AN: 2222

European-Finnish (FIN) AF: 0.00116 AC: 5 AN: 4321

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 194

European-Non Finnish (NFE) AF: 0.0000207 AC: 1 AN: 48301

Other (OTH) AF: 0.00 AC: 0 AN: 1316

⚠️ 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.

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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs370976127; hg19: chrX-106062175;