rs151102993
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001080414.4(CCDC88C):c.4621C>T(p.Arg1541Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,613,296 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 3 hom. )
Consequence
CCDC88C
NM_001080414.4 missense
NM_001080414.4 missense
Scores
3
14
Clinical Significance
Conservation
PhyloP100: 2.76
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0054469407).
BP6
?
Variant 14-91283338-G-A is Benign according to our data. Variant chr14-91283338-G-A is described in ClinVar as [Benign]. Clinvar id is 158113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000446 (68/152334) while in subpopulation EAS AF= 0.0106 (55/5190). AF 95% confidence interval is 0.00836. There are 0 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 3 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC88C | NM_001080414.4 | c.4621C>T | p.Arg1541Cys | missense_variant | 26/30 | ENST00000389857.11 | |
CCDC88C | XM_011536796.3 | c.4513C>T | p.Arg1505Cys | missense_variant | 26/30 | ||
CCDC88C | XM_047431418.1 | c.4354C>T | p.Arg1452Cys | missense_variant | 23/27 | ||
CCDC88C | XM_047431419.1 | c.4621C>T | p.Arg1541Cys | missense_variant | 26/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC88C | ENST00000389857.11 | c.4621C>T | p.Arg1541Cys | missense_variant | 26/30 | 5 | NM_001080414.4 | P1 | |
CCDC88C | ENST00000334448.5 | n.286C>T | non_coding_transcript_exon_variant | 1/6 | 1 | ||||
CCDC88C | ENST00000556726.5 | c.*455C>T | 3_prime_UTR_variant | 3/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000447 AC: 68AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00124 AC: 305AN: 246376Hom.: 3 AF XY: 0.00122 AC XY: 163AN XY: 134000
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GnomAD4 exome AF: 0.000318 AC: 464AN: 1460962Hom.: 3 Cov.: 31 AF XY: 0.000323 AC XY: 235AN XY: 726678
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GnomAD4 genome ? AF: 0.000446 AC: 68AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.000550 AC XY: 41AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 15, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
0.088
.;B
Vest4
MVP
MPC
0.19
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at