chrX-18642018-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate
The NM_000330.4(RS1):c.661A>G(p.Ser221Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,209,888 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000330.4 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 |
---|---|---|---|---|---|---|---|
RS1 | NM_000330.4 | c.661A>G | p.Ser221Gly | missense_variant | 6/6 | ENST00000379984.4 | |
RS1 | XM_047442337.1 | c.565A>G | p.Ser189Gly | missense_variant | 4/4 | ||
CDKL5 | NM_001037343.2 | c.2714-3989T>C | intron_variant | ||||
CDKL5 | NM_003159.3 | c.2714-3989T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RS1 | ENST00000379984.4 | c.661A>G | p.Ser221Gly | missense_variant | 6/6 | 1 | NM_000330.4 | P1 | |
CDKL5 | ENST00000379989.6 | c.2714-3989T>C | intron_variant | 1 | |||||
CDKL5 | ENST00000379996.7 | c.2714-3989T>C | intron_variant | 1 | |||||
RS1 | ENST00000476595.1 | n.1152A>G | non_coding_transcript_exon_variant | 5/5 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000446 AC: 5AN: 112091Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34271
GnomAD3 exomes AF: 0.00000547 AC: 1AN: 182869Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67505
GnomAD4 exome AF: 0.0000100 AC: 11AN: 1097797Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 5AN XY: 363311
GnomAD4 genome ? AF: 0.0000446 AC: 5AN: 112091Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34271
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 221 of the RS1 protein (p.Ser221Gly). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with RS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1404057). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RS1 protein function with a negative predictive value of 95%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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