2-224481929-T-C
Variant summary
Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_003590.5(CUL3):c.1992A>G(p.Gln664Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,588,794 control chromosomes in the GnomAD database, including 20,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_003590.5 synonymous
Scores
Clinical Significance
Conservation
Publications
- complex neurodevelopmental disorderInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- neurodevelopmental disorder with or without autism or seizuresInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- pseudohypoaldosteronism type 2EInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
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ACMG classification
Our verdict: Benign. The variant received -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CUL3 | NM_003590.5 | c.1992A>G | p.Gln664Gln | synonymous_variant | Exon 14 of 16 | ENST00000264414.9 | NP_003581.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.185 AC: 28047AN: 151926Hom.: 2922 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.184 AC: 43668AN: 237076 AF XY: 0.182 show subpopulations
GnomAD4 exome AF: 0.149 AC: 214367AN: 1436750Hom.: 17969 Cov.: 30 AF XY: 0.151 AC XY: 108058AN XY: 713414 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.185 AC: 28090AN: 152044Hom.: 2932 Cov.: 32 AF XY: 0.188 AC XY: 13994AN XY: 74302 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Benign:3
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not specified Benign:1
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Autosomal dominant pseudohypoaldosteronism type 1 Benign:1
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Pseudohypoaldosteronism type 2E Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at