rs13059238
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_024513.4(FYCO1):c.3001A>G(p.Asn1001Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,892 control chromosomes in the GnomAD database, including 14,017 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1001E) has been classified as Likely benign.
Frequency
Consequence
NM_024513.4 missense
Scores
Clinical Significance
Conservation
Publications
- cataract 18Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- early-onset nuclear cataractInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- total early-onset cataractInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| FYCO1 | NM_024513.4 | c.3001A>G | p.Asn1001Asp | missense_variant | Exon 8 of 18 | ENST00000296137.7 | NP_078789.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| FYCO1 | ENST00000296137.7 | c.3001A>G | p.Asn1001Asp | missense_variant | Exon 8 of 18 | 1 | NM_024513.4 | ENSP00000296137.2 |
Frequencies
GnomAD3 genomes AF: 0.0934 AC: 14209AN: 152086Hom.: 1008 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.127 AC: 31697AN: 249768 AF XY: 0.142 show subpopulations
GnomAD4 exome AF: 0.117 AC: 170442AN: 1461688Hom.: 13010 Cov.: 37 AF XY: 0.125 AC XY: 90798AN XY: 727162 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0933 AC: 14205AN: 152204Hom.: 1007 Cov.: 33 AF XY: 0.0989 AC XY: 7360AN XY: 74420 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Cataract 18 Benign:3
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. -
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not provided Benign:2
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
not specified Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at