rs149797560
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001376256.1(CRYM):c.8G>T(p.Arg3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,584,580 control chromosomes in the GnomAD database, including 2 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001376256.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRYM | NM_001376256.1 | c.8G>T | p.Arg3Leu | missense_variant | 1/8 | ENST00000572914.2 | |
CRYM | NM_001888.5 | c.8G>T | p.Arg3Leu | missense_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRYM | ENST00000572914.2 | c.8G>T | p.Arg3Leu | missense_variant | 1/8 | 2 | NM_001376256.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000230 AC: 35AN: 152190Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000184 AC: 38AN: 206782Hom.: 0 AF XY: 0.000170 AC XY: 19AN XY: 111970
GnomAD4 exome AF: 0.000103 AC: 148AN: 1432272Hom.: 1 Cov.: 32 AF XY: 0.000128 AC XY: 91AN XY: 710568
GnomAD4 genome ? AF: 0.000223 AC: 34AN: 152308Hom.: 1 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74470
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 18, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 17, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 21, 2023 | An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 3 of the CRYM protein (p.Arg3Leu). ClinVar contains an entry for this variant (Variation ID: 289303). This variant has not been reported in the literature in individuals affected with CRYM-related conditions. This variant is present in population databases (rs149797560, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jan 24, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at