X-106818945-GTT-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_017752.3(TBC1D8B):​c.241+187_241+188delTT 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 0.00017 (0 hom., 2 hem., cov: 19)
• Consequence: TBC1D8B NM_017752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000172 (17/98978) while in subpopulation AFR AF = 0.000585 (16/27353). AF 95% confidence interval is 0.000366. There are 0 homozygotes in GnomAd4. There are 2 alleles in the male GnomAd4 subpopulation. Median coverage is 19. This position passed quality control check.
• BS2: High AC in GnomAd4 at 17 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D8B	NM_017752.3	c.241+187_241+188delTT		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+173_241+174delTT		intron_variant	Intron 2 of 20	1	NM_017752.3	ENSP00000349781.5

Frequencies

GnomAD3 genomes AF: 0.000172 AC: 17 AN: 98988 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.000586

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: 0.000231

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000172 AC: 17 AN: 98978 Hom.: 0 Cov.: 19 AF XY: 0.0000769 AC XY: 2 AN XY: 26002

African (AFR) AF: 0.000585 AC: 16 AN: 27353

American (AMR) AF: 0.00 AC: 0 AN: 9069

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2422

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

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

European-Finnish (FIN) AF: 0.000231 AC: 1 AN: 4320

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 48300

Other (OTH) AF: 0.00 AC: 0 AN: 1314

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism

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;