Variant 2-108791765-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_144978.3(CCDC138):c.357G>A(p.Ser119Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000884 in 1,599,060 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 2 hom. )

Consequence

CCDC138
NM_144978.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0990

Variant links:

Genes affected

CCDC138 (HGNC:26531): (coiled-coil domain containing 138)

CCDC138 links:

RANBP2 (HGNC:9848): (RAN binding protein 2) RAN is a small GTP-binding protein of the RAS superfamily that is associated with the nuclear membrane and is thought to control a variety of cellular functions through its interactions with other proteins. This gene encodes a very large RAN-binding protein that immunolocalizes to the nuclear pore complex. The protein is a giant scaffold and mosaic cyclophilin-related nucleoporin implicated in the Ran-GTPase cycle. The encoded protein directly interacts with the E2 enzyme UBC9 and strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100. These findings place sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on chromosome 2q. [provided by RefSeq, Jul 2008]

RANBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 2-108791765-G-A is Benign according to our data. Variant chr2-108791765-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651256.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.099 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC138	NM_144978.3 link	c.357G>A	p.Ser119Ser	synonymous_variant	4/15	ENST00000295124.9	NP_659415.1	Q96M89-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC138	ENST00000295124.9 link	c.357G>A	p.Ser119Ser	synonymous_variant	4/15	2	NM_144978.3	ENSP00000295124.4		Q96M89-1

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

400

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00778

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000473

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00107

AC:

263

AN:

244690

Hom.:

AF XY:

0.000885

AC XY:

117

AN XY:

132150

show subpopulations

Gnomad AFR exome

AF:

0.00818

Gnomad AMR exome

AF:

0.000596

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000386

Gnomad SAS exome

AF:

0.000493

Gnomad FIN exome

AF:

0.000335

Gnomad NFE exome

AF:

0.000732

Gnomad OTH exome

AF:

0.000665

GnomAD4 exome

AF:

0.000699

AC:

1012

AN:

1446912

Hom.:

Cov.:

AF XY:

0.000686

AC XY:

494

AN XY:

719642

show subpopulations

Gnomad4 AFR exome

AF:

0.00901

Gnomad4 AMR exome

AF:

0.000753

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000178

Gnomad4 SAS exome

AF:

0.000346

Gnomad4 FIN exome

AF:

0.000420

Gnomad4 NFE exome

AF:

0.000510

Gnomad4 OTH exome

AF:

0.000986

GnomAD4 genome

AF:

0.00264

AC:

401

AN:

152148

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

199

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00778

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000473

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.00297

Asia WGS

AF:

0.00116

AC:

AN:

3470

EpiCase

AF:

0.000710

EpiControl

AF:

0.000534

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

CCDC138: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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