NM_017752.3:c.225C>T

Variant names:

• chrX-106818757-C-T
• rs147207846
• NM_017752.3:c.225C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_017752.3(TBC1D8B):​c.225C>T​(p.Tyr75Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000368 in 1,197,151 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.000036 (0 hom. 15 hem.)
• Consequence: TBC1D8B NM_017752.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.59
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant X-106818757-C-T is Benign according to our data. Variant chrX-106818757-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2415277.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.6 with no splicing effect.
• BS2: High AC in GnomAd4 at 5 XL,AD gene.

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.225C>T	p.Tyr75Tyr	synonymous	Exon 2 of 21	NP_060222.2
	TBC1D8B	NM_001441214.1		c.225C>T	p.Tyr75Tyr	synonymous	Exon 2 of 20	NP_001428143.1
	TBC1D8B	NM_198881.2		c.225C>T	p.Tyr75Tyr	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.225C>T	p.Tyr75Tyr	synonymous	Exon 2 of 21	ENSP00000349781.5	Q0IIM8-1
	TBC1D8B	ENST00000310452.6	TSL:1	c.225C>T	p.Tyr75Tyr	synonymous	Exon 2 of 12	ENSP00000310675.2	Q0IIM8-3
	TBC1D8B	ENST00000481617.6	TSL:1	c.225C>T	p.Tyr75Tyr	synonymous	Exon 2 of 7	ENSP00000421375.1	D6RFZ2

Frequencies

GnomAD3 genomes AF: 0.0000452 AC: 5 AN: 110530 Hom.: 0 Cov.: 22

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000949

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000723 AC: 13 AN: 179737 AF XY: 0.0000773

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000161

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000359 AC: 39 AN: 1086621 Hom.: 0 Cov.: 27 AF XY: 0.0000425 AC XY: 15 AN XY: 353299

African (AFR) AF: 0.00 AC: 0 AN: 26086

American (AMR) AF: 0.00 AC: 0 AN: 34960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19190

East Asian (EAS) AF: 0.00 AC: 0 AN: 30075

South Asian (SAS) AF: 0.00 AC: 0 AN: 53246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40171

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4087

European-Non Finnish (NFE) AF: 0.0000444 AC: 37 AN: 833109

Other (OTH) AF: 0.0000438 AC: 2 AN: 45697

GnomAD4 genome AF: 0.0000452 AC: 5 AN: 110530 Hom.: 0 Cov.: 22 AF XY: 0.0000608 AC XY: 2 AN XY: 32898

African (AFR) AF: 0.00 AC: 0 AN: 30497

American (AMR) AF: 0.00 AC: 0 AN: 10292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2621

East Asian (EAS) AF: 0.00 AC: 0 AN: 3544

South Asian (SAS) AF: 0.00 AC: 0 AN: 2622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5877

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000949 AC: 5 AN: 52673

Other (OTH) AF: 0.00 AC: 0 AN: 1478

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000793

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.3
DANN	Benign	0.73
PhyloP100		1.6
PromoterAI		-0.0092	Neutral
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: rs147207846; hg19: chrX-106061987;