rs201414940
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_001080414.4(CCDC88C):āc.4579A>Gā(p.Thr1527Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,613,492 control chromosomes in the GnomAD database, including 1 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001080414.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC88C | NM_001080414.4 | c.4579A>G | p.Thr1527Ala | missense_variant | 26/30 | ENST00000389857.11 | |
CCDC88C | XM_011536796.3 | c.4471A>G | p.Thr1491Ala | missense_variant | 26/30 | ||
CCDC88C | XM_047431418.1 | c.4312A>G | p.Thr1438Ala | missense_variant | 23/27 | ||
CCDC88C | XM_047431419.1 | c.4579A>G | p.Thr1527Ala | missense_variant | 26/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC88C | ENST00000389857.11 | c.4579A>G | p.Thr1527Ala | missense_variant | 26/30 | 5 | NM_001080414.4 | P1 | |
CCDC88C | ENST00000334448.5 | n.244A>G | non_coding_transcript_exon_variant | 1/6 | 1 | ||||
CCDC88C | ENST00000556726.5 | c.*413A>G | 3_prime_UTR_variant | 3/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000507 AC: 77AN: 151982Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000109 AC: 27AN: 247488Hom.: 0 AF XY: 0.0000520 AC XY: 7AN XY: 134624
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461510Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727032
GnomAD4 genome ? AF: 0.000507 AC: 77AN: 151982Hom.: 1 Cov.: 32 AF XY: 0.000499 AC XY: 37AN XY: 74222
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hydrocephalus, nonsyndromic, autosomal recessive 1;C4518336:Spinocerebellar ataxia type 40 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 17, 2019 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
CCDC88C-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 23, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at