NM_001080414.4:c.3393G>T

Variant names:

Variant summary

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

The NM_001080414.4(CCDC88C):c.3393G>T(p.Ala1131Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,608,956 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A1131A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.018 ( 75 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 64 hom. )

Consequence

CCDC88C
NM_001080414.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.73

Publications

0 publications found

Variant links:

Genes affected

CCDC88C (HGNC:19967): (coiled-coil domain containing 88C) This gene encodes a ubiquitously expressed coiled-coil domain-containing protein that interacts with the dishevelled protein and is a negative regulator of the Wnt signalling pathway. The protein encoded by this gene has a PDZ-domain binding motif in its C-terminus with which it interacts with the dishevelled protein. Dishevelled is a scaffold protein involved in the regulation of the Wnt signaling pathway. The Wnt signaling pathway plays an important role in embryonic development, tissue maintenance, and cancer progression. Mutations in this gene cause autosomal recessive, primary non-syndromic congenital hydrocephalus; a condition characterized by excessive accumulation of cerebrospinal fluid in the ventricles of the brain. [provided by RefSeq, Jan 2013]

CCDC88C Gene-Disease associations (from GenCC):

hydrocephalus, nonsyndromic, autosomal recessive 1
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
spinocerebellar ataxia type 40
Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

CCDC88C 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=-0.44).

BP6

Variant 14-91303943-C-A is Benign according to our data. Variant chr14-91303943-C-A is described in ClinVar as Benign. ClinVar VariationId is 158108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 link	c.3393G>T	p.Ala1131Ala	synonymous_variant	Exon 20 of 30	ENST00000389857.11	NP_001073883.2	Q9P219-1B4DZB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11 link	c.3393G>T	p.Ala1131Ala	synonymous_variant	Exon 20 of 30	5	NM_001080414.4	ENSP00000374507.6		Q9P219-1

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2699

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0615

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00693

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.00447

AC:

1095

AN:

245204

AF XY:

0.00329

show subpopulations

Gnomad AFR exome

AF:

0.0620

Gnomad AMR exome

AF:

0.00310

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.00233

GnomAD4 exome

AF:

0.00179

AC:

2609

AN:

1456622

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1098

AN XY:

724734

show subpopulations

African (AFR)

AF:

0.0623

AC:

2084

AN:

33456

American (AMR)

AF:

0.00347

AC:

155

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49234

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000114

AC:

127

AN:

1111134

Other (OTH)

AF:

0.00380

AC:

229

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

144

289

433

578

722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0177

AC:

2700

AN:

152334

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1255

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0614

AC:

2550

AN:

41564

American (AMR)

AF:

0.00693

AC:

106

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68040

Other (OTH)

AF:

0.0147

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

133

266

398

531

664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00656

Hom.:

Bravo

AF:

0.0193

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 20, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Apr 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CCDC88C-related disorder

Benign:1

Jun 19, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.059

(source)

DANN

Benign

0.71

PhyloP100

-2.7

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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