chr22-50523648-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_005138.3(SCO2):c.764G>T(p.Arg255Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R255Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_005138.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCO2 | NM_005138.3 | c.764G>T | p.Arg255Leu | missense_variant | 2/2 | ENST00000395693.8 | |
NCAPH2 | NM_152299.4 | c.*273C>A | 3_prime_UTR_variant | 20/20 | ENST00000420993.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCO2 | ENST00000395693.8 | c.764G>T | p.Arg255Leu | missense_variant | 2/2 | 1 | NM_005138.3 | P1 | |
NCAPH2 | ENST00000420993.7 | c.*273C>A | 3_prime_UTR_variant | 20/20 | 1 | NM_152299.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152218Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251258Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135856
GnomAD4 exome AF: 0.0000445 AC: 65AN: 1461586Hom.: 0 Cov.: 35 AF XY: 0.0000330 AC XY: 24AN XY: 727102
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152218Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74374
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 01, 2022 | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 255 of the SCO2 protein (p.Arg255Leu). This variant is present in population databases (rs368908383, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with SCO2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1163688). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 08, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at