rs6523896

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.977

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D8B	NM_017752.3 link	c.162G>A	p.Leu54Leu	synonymous_variant	Exon 2 of 21	ENST00000357242.10	NP_060222.2	Q0IIM8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D8B	ENST00000357242.10 link	c.162G>A	p.Leu54Leu	synonymous_variant	Exon 2 of 21	1	NM_017752.3	ENSP00000349781.5		Q0IIM8-1

Frequencies

GnomAD3 genomes

AF:

0.0643

AC:

7095

AN:

110336

Hom.:

597

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00573

AC XY:

2069

AN XY:

361059

show subpopulations

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:

AN:

19274

East Asian (EAS)

AF:

0.00

AC:

AN:

30103

South Asian (SAS)

AF:

0.000969

AC:

AN:

53636

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40369

Middle Eastern (MID)

AF:

0.0107

AC:

AN:

4115

European-Non Finnish (NFE)

AF:

0.000294

AC:

247

AN:

840107

Other (OTH)

AF:

0.0178

AC:

816

AN:

45916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

209

417

626

834

1043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0645

AC:

7120

AN:

110389

Hom.:

599

Cov.:

AF XY:

0.0589

AC XY:

1933

AN XY:

32821

show subpopulations

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:

AN:

2633

East Asian (EAS)

AF:

0.00

AC:

AN:

3522

South Asian (SAS)

AF:

0.00152

AC:

AN:

2623

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5905

Middle Eastern (MID)

AF:

0.00939

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.000684

AC:

AN:

52661

Other (OTH)

AF:

0.0498

AC:

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

199

398

598

797

996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0332

Hom.:

289

Bravo

AF:

0.0746

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 27, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

6.3

(source)

DANN

Benign

0.65

PhyloP100

0.98

PromoterAI

-0.023

Neutral

(source)

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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rs6523896

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over