Variant X-106821115-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017752.3(TBC1D8B):c.360+120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 400,985 control chromosomes in the GnomAD database, including 733 homozygotes. There are 2,406 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 550 hom., 1869 hem., cov: 22)

Exomes 𝑓: 0.0081 ( 183 hom. 537 hem. )

Consequence

TBC1D8B
NM_017752.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.633

Variant links:

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]

TBC1D8B links:

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]

MORC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-106821115-C-T is Benign according to our data. Variant chrX-106821115-C-T is described in ClinVar as [Benign]. Clinvar id is 1253489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D8B	NM_017752.3 linkuse as main transcript	c.360+120C>T		intron_variant		ENST00000357242.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D8B	ENST00000357242.10 linkuse as main transcript	c.360+120C>T		intron_variant		1	NM_017752.3	P2	Q0IIM8-1

Frequencies

GnomAD3 genomes

AF:

0.0616

AC:

6816

AN:

110648

Hom.:

548

Cov.:

AF XY:

0.0559

AC XY:

1849

AN XY:

33060

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0246

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00150

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00844

Gnomad NFE

AF:

0.000569

Gnomad OTH

AF:

0.0480

GnomAD4 exome

AF:

0.00806

AC:

2341

AN:

290287

Hom.:

183

AF XY:

0.00668

AC XY:

537

AN XY:

80415

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.0142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000396

Gnomad4 OTH exome

AF:

0.0208

GnomAD4 genome

AF:

0.0618

AC:

6840

AN:

110698

Hom.:

550

Cov.:

AF XY:

0.0564

AC XY:

1869

AN XY:

33120

show subpopulations

Gnomad4 AFR

AF:

0.213

Gnomad4 AMR

AF:

0.0245

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00113

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000569

Gnomad4 OTH

AF:

0.0474

Alfa

AF:

0.0474

Hom.:

181

Bravo

AF:

0.0717

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 22, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.3

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over