14-91359660-C-T

Position:

chr14-91359660-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001080414.4(CCDC88C):c.322G>A(p.Gly108Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000462 in 1,608,390 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00048 ( 0 hom. )

Consequence

CCDC88C
NM_001080414.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:1

Conservation

PhyloP100: 4.67

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 links:

CCDC88C (HGNC:):

CCDC88C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 linkuse as main transcript	c.322G>A	p.Gly108Ser	missense_variant	4/30	ENST00000389857.11	NP_001073883.2	Q9P219-1B4DZB8
CCDC88C	XM_011536796.3 linkuse as main transcript	c.214G>A	p.Gly72Ser	missense_variant	4/30		XP_011535098.1
CCDC88C	XM_047431419.1 linkuse as main transcript	c.322G>A	p.Gly108Ser	missense_variant	4/28
CCDC88C	XM_005267691.6 linkuse as main transcript	c.322G>A	p.Gly108Ser	missense_variant	4/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC88C	ENST00000389857.11 linkuse as main transcript	c.322G>A	p.Gly108Ser	missense_variant	4/30	5	NM_001080414.4	ENSP00000374507.6	Q9P219-1
CCDC88C	ENST00000553437.1 linkuse as main transcript	n.152G>A		non_coding_transcript_exon_variant	2/4	2
CCDC88C	ENST00000554872.5 linkuse as main transcript	n.262G>A		non_coding_transcript_exon_variant	3/7	4

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000221

AC:

AN:

240144

Hom.:

AF XY:

0.000231

AC XY:

AN XY:

129794

show subpopulations

Gnomad AFR exome

AF:

0.0000693

Gnomad AMR exome

AF:

0.0000893

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.000482

AC:

702

AN:

1456208

Hom.:

Cov.:

AF XY:

0.000466

AC XY:

337

AN XY:

723538

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000584

Gnomad4 OTH exome

AF:

0.000714

GnomAD4 genome

AF:

0.000269

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000575

Hom.:

Bravo

AF:

0.000446

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000606

AC:

ExAC

AF:

0.000174

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:3

Uncertain significance, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2018	- -
Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Oct 13, 2023	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 04, 2022	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 108 of the CCDC88C protein (p.Gly108Ser). This variant is present in population databases (rs61745604, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with CCDC88C-related conditions. ClinVar contains an entry for this variant (Variation ID: 158106). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 02, 2018

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0049

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.16

Sift

Benign

0.095

Sift4G

Benign

0.12

Polyphen

0.94

Vest4

0.73

MVP

0.50

MPC

0.53

ClinPred

0.15

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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