rs61745604

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001080414.4(CCDC88C):​c.322G>T​(p.Gly108Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CCDC88C
NM_001080414.4 missense

Scores

6
9
4

Clinical Significance

Not reported in ClinVar

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC88CNM_001080414.4 linkuse as main transcriptc.322G>T p.Gly108Cys missense_variant 4/30 ENST00000389857.11 NP_001073883.2 Q9P219-1B4DZB8
CCDC88CXM_011536796.3 linkuse as main transcriptc.214G>T p.Gly72Cys missense_variant 4/30 XP_011535098.1
CCDC88CXM_047431419.1 linkuse as main transcriptc.322G>T p.Gly108Cys missense_variant 4/28
CCDC88CXM_005267691.6 linkuse as main transcriptc.322G>T p.Gly108Cys missense_variant 4/26

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC88CENST00000389857.11 linkuse as main transcriptc.322G>T p.Gly108Cys missense_variant 4/305 NM_001080414.4 ENSP00000374507.6 Q9P219-1
CCDC88CENST00000553437.1 linkuse as main transcriptn.152G>T non_coding_transcript_exon_variant 2/42
CCDC88CENST00000554872.5 linkuse as main transcriptn.262G>T non_coding_transcript_exon_variant 3/74

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1456208
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
723538
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.013
T
MetaRNN
Pathogenic
0.87
D
MetaSVM
Benign
-0.87
T
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-5.7
D
REVEL
Uncertain
0.38
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0050
D
Polyphen
1.0
D
Vest4
0.90
MutPred
0.65
Gain of catalytic residue at M106 (P = 2e-04);
MVP
0.60
MPC
0.62
ClinPred
0.99
D
GERP RS
5.5
Varity_R
0.67
gMVP
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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.

Other links and lift over

dbSNP: rs61745604; hg19: chr14-91826004; API