NM_001080414.4:c.5975T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080414.4(CCDC88C):c.5975T>C(p.Leu1992Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,609,524 control chromosomes in the GnomAD database, including 629,801 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.90 ( 61983 hom., cov: 34)

Exomes 𝑓: 0.88 ( 567818 hom. )

Consequence

CCDC88C
NM_001080414.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.254

Publications

34 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.007662E-7).

BP6

Variant 14-91272737-A-G is Benign according to our data. Variant chr14-91272737-A-G is described in ClinVar as Benign. ClinVar VariationId is 158118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 link	c.5975T>C	p.Leu1992Pro	missense_variant	Exon 30 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.5975T>C	p.Leu1992Pro	missense_variant	Exon 30 of 30	5	NM_001080414.4	ENSP00000374507.6		Q9P219-1
CCDC88C	ENST00000556726.5 link	c.*1809T>C		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000452406.1		H0YJX5

Frequencies

GnomAD3 genomes

AF:

0.898

AC:

136665

AN:

152166

Hom.:

61928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.979

Gnomad AMI

AF:

0.901

Gnomad AMR

AF:

0.818

Gnomad ASJ

AF:

0.855

Gnomad EAS

AF:

0.586

Gnomad SAS

AF:

0.731

Gnomad FIN

AF:

0.948

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.898

Gnomad OTH

AF:

0.870

GnomAD2 exomes

AF:

0.846

AC:

204013

AN:

241008

AF XY:

0.844

show subpopulations

Gnomad AFR exome

AF:

0.981

Gnomad AMR exome

AF:

0.793

Gnomad ASJ exome

AF:

0.861

Gnomad EAS exome

AF:

0.575

Gnomad FIN exome

AF:

0.947

Gnomad NFE exome

AF:

0.896

Gnomad OTH exome

AF:

0.860

GnomAD4 exome

AF:

0.880

AC:

1282470

AN:

1457240

Hom.:

567818

Cov.:

AF XY:

0.876

AC XY:

634881

AN XY:

724928

show subpopulations

African (AFR)

AF:

0.983

AC:

32894

AN:

33464

American (AMR)

AF:

0.792

AC:

35352

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.863

AC:

22530

AN:

26092

East Asian (EAS)

AF:

0.605

AC:

24013

AN:

39680

South Asian (SAS)

AF:

0.748

AC:

64433

AN:

86122

European-Finnish (FIN)

AF:

0.944

AC:

47149

AN:

49972

Middle Eastern (MID)

AF:

0.858

AC:

4856

AN:

5662

European-Non Finnish (NFE)

AF:

0.899

AC:

998810

AN:

1111344

Other (OTH)

AF:

0.870

AC:

52433

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

9318

18635

27953

37270

46588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21386

42772

64158

85544

106930

<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:

0.898

AC:

136779

AN:

152284

Hom.:

61983

Cov.:

AF XY:

0.893

AC XY:

66512

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.979

AC:

40702

AN:

41594

American (AMR)

AF:

0.818

AC:

12509

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.855

AC:

2967

AN:

3472

East Asian (EAS)

AF:

0.586

AC:

3014

AN:

5140

South Asian (SAS)

AF:

0.730

AC:

3522

AN:

4824

European-Finnish (FIN)

AF:

0.948

AC:

10067

AN:

10620

Middle Eastern (MID)

AF:

0.874

AC:

257

AN:

294

European-Non Finnish (NFE)

AF:

0.898

AC:

61080

AN:

68016

Other (OTH)

AF:

0.870

AC:

1839

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

686

1372

2057

2743

3429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.883

Hom.:

155699

Bravo

AF:

0.894

TwinsUK

AF:

0.894

AC:

3314

ALSPAC

AF:

0.903

AC:

3480

ESP6500AA

AF:

0.976

AC:

3605

ESP6500EA

AF:

0.899

AC:

7322

ExAC

AF:

0.851

AC:

102108

Asia WGS

AF:

0.691

AC:

2406

AN:

3478

EpiCase

AF:

0.884

EpiControl

AF:

0.883

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 29, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spinocerebellar ataxia type 40

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hydrocephalus, nonsyndromic, autosomal recessive 1

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.6

(source)

DANN

Benign

0.20

DEOGEN2

Benign

0.0020

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.073

T;T

MetaRNN

Benign

9.0e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

.;N

PhyloP100

-0.25

PrimateAI

Benign

0.28

PROVEAN

Benign

1.9

.;N

REVEL

Benign

0.0060

Sift

Benign

0.42

.;T

Sift4G

Benign

0.32

T;T

Polyphen

0.0

.;B

Vest4

0.017

MPC

0.21

ClinPred

0.0022

GERP RS

-2.6

Varity_R

0.043

gMVP

0.069

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

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