X-106818560-A-G

Variant names:

• chrX-106818560-A-G
• rs12009983
• NM_017752.3:c.131-103A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017752.3(TBC1D8B):​c.131-103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00426 in 539,957 control chromosomes in the GnomAD database, including 47 homozygotes. There are 620 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (34 hom., 459 hem., cov: 22)
  • Exomes 𝑓: 0.0015 (13 hom. 161 hem.)
• Consequence: TBC1D8B NM_017752.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.76

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-106818560-A-G is Benign according to our data. Variant chrX-106818560-A-G is described in ClinVar as [Benign]. Clinvar id is 1226609.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0147 (1643/111398) while in subpopulation AFR AF= 0.0507 (1562/30788). AF 95% confidence interval is 0.0486. There are 34 homozygotes in gnomad4. There are 459 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 34 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D8B	NM_017752.3	c.131-103A>G		intron_variant	Intron 1 of 20	ENST00000357242.10	NP_060222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D8B	ENST00000357242.10	c.131-103A>G		intron_variant	Intron 1 of 20	1	NM_017752.3	ENSP00000349781.5

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 1639 AN: 111348 Hom.: 34 Cov.: 22 AF XY: 0.0136 AC XY: 457 AN XY: 33678

Gnomad AFR AF: 0.0507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00535

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00847

Gnomad NFE AF: 0.000189

Gnomad OTH AF: 0.00874

GnomAD4 exome AF: 0.00153 AC: 657 AN: 428559 Hom.: 13 Cov.: 7 AF XY: 0.00153 AC XY: 161 AN XY: 104993

Gnomad4 AFR exome AF: 0.0485

Gnomad4 AMR exome AF: 0.00292

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000312

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000105

Gnomad4 OTH exome AF: 0.00367

GnomAD4 genome AF: 0.0147 AC: 1643 AN: 111398 Hom.: 34 Cov.: 22 AF XY: 0.0136 AC XY: 459 AN XY: 33738

Gnomad4 AFR AF: 0.0507

Gnomad4 AMR AF: 0.00535

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000189

Gnomad4 OTH AF: 0.00863

Alfa AF: 0.0134 Hom.: 59

Bravo AF: 0.0174

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
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs12009983; hg19: chrX-106061790;