chrX-106818694-G-A

Variant names:

• chrX-106818694-G-A
• rs6523896
• NM_017752.3:c.162G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_017752.3(TBC1D8B):​c.162G>A​(p.Leu54Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,205,206 control chromosomes in the GnomAD database, including 1,192 homozygotes. There are 4,002 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (599 hom., 1933 hem., cov: 22)
  • Exomes 𝑓: 0.0070 (593 hom. 2069 hem.)
• Consequence: TBC1D8B NM_017752.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.977
• Publications: 1 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant X-106818694-G-A is Benign according to our data. Variant chrX-106818694-G-A is described in ClinVar as Benign. ClinVar VariationId is 1294550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.977 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017752.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D8B	NM_017752.3	MANE Select	c.162G>A	p.Leu54Leu	synonymous	Exon 2 of 21	NP_060222.2
	TBC1D8B	NM_001441214.1		c.162G>A	p.Leu54Leu	synonymous	Exon 2 of 20	NP_001428143.1
	TBC1D8B	NM_198881.2		c.162G>A	p.Leu54Leu	synonymous	Exon 2 of 12	NP_942582.1	Q0IIM8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D8B	ENST00000357242.10	TSL:1 MANE Select	c.162G>A	p.Leu54Leu	synonymous	Exon 2 of 21	ENSP00000349781.5	Q0IIM8-1
	TBC1D8B	ENST00000310452.6	TSL:1	c.162G>A	p.Leu54Leu	synonymous	Exon 2 of 12	ENSP00000310675.2	Q0IIM8-3
	TBC1D8B	ENST00000481617.6	TSL:1	c.162G>A	p.Leu54Leu	synonymous	Exon 2 of 7	ENSP00000421375.1	D6RFZ2

Frequencies

GnomAD3 genomes AF: 0.0643 AC: 7095 AN: 110336 Hom.: 597 Cov.: 22

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00190

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00851

Gnomad NFE AF: 0.000684

Gnomad OTH AF: 0.0505

GnomAD2 exomes AF: 0.0185 AC: 3337 AN: 180333 AF XY: 0.0116

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.00921

Gnomad ASJ exome AF: 0.000135

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000421

Gnomad OTH exome AF: 0.00927

GnomAD4 exome AF: 0.00704 AC: 7708 AN: 1094817 Hom.: 593 Cov.: 28 AF XY: 0.00573 AC XY: 2069 AN XY: 361059

African (AFR) AF: 0.234 AC: 6147 AN: 26261

American (AMR) AF: 0.0114 AC: 401 AN: 35036

Ashkenazi Jewish (ASJ) AF: 0.0000519 AC: 1 AN: 19274

East Asian (EAS) AF: 0.00 AC: 0 AN: 30103

South Asian (SAS) AF: 0.000969 AC: 52 AN: 53636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40369

Middle Eastern (MID) AF: 0.0107 AC: 44 AN: 4115

European-Non Finnish (NFE) AF: 0.000294 AC: 247 AN: 840107

Other (OTH) AF: 0.0178 AC: 816 AN: 45916

GnomAD4 genome AF: 0.0645 AC: 7120 AN: 110389 Hom.: 599 Cov.: 22 AF XY: 0.0589 AC XY: 1933 AN XY: 32821

African (AFR) AF: 0.222 AC: 6740 AN: 30356

American (AMR) AF: 0.0256 AC: 263 AN: 10290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2633

East Asian (EAS) AF: 0.00 AC: 0 AN: 3522

South Asian (SAS) AF: 0.00152 AC: 4 AN: 2623

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5905

Middle Eastern (MID) AF: 0.00939 AC: 2 AN: 213

European-Non Finnish (NFE) AF: 0.000684 AC: 36 AN: 52661

Other (OTH) AF: 0.0498 AC: 75 AN: 1506

Alfa AF: 0.0332 Hom.: 289

Bravo AF: 0.0746

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.3
DANN	Benign	0.65
PhyloP100		0.98
PromoterAI		-0.023	Neutral
Mutation Taster		=96/4	polymorphism (auto)

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: rs6523896; hg19: chrX-106061924;