rs762200707
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PM5BS1_SupportingBS2
The NM_006891.4(CRYGD):āc.155C>Gā(p.Ser52Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000525 in 152,270 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S52P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_006891.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRYGD | NM_006891.4 | c.155C>G | p.Ser52Trp | missense_variant | 2/3 | ENST00000264376.5 | |
LOC100507443 | NR_038437.1 | n.97+4984G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRYGD | ENST00000264376.5 | c.155C>G | p.Ser52Trp | missense_variant | 2/3 | 1 | NM_006891.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152152Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000106 AC: 26AN: 246370Hom.: 0 AF XY: 0.000119 AC XY: 16AN XY: 134302
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000980 AC: 143AN: 1459244Hom.: 0 Cov.: 30 AF XY: 0.0000951 AC XY: 69AN XY: 725900
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152270Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74448
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2021 | The c.155C>G (p.S52W) alteration is located in exon 2 (coding exon 2) of the CRYGD gene. This alteration results from a C to G substitution at nucleotide position 155, causing the serine (S) at amino acid position 52 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Aculeiform cataract Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | This sequence change replaces serine with tryptophan at codon 52 of the CRYGD protein (p.Ser52Trp). The serine residue is weakly conserved and there is a large physicochemical difference between serine and tryptophan. This variant is present in population databases (rs762200707, ExAC 0.07%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals affected with CRYGD-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at