rs984016152
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014425.5(INVS):c.2428C>T(p.Arg810Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R810H) has been classified as Uncertain significance.
Frequency
Consequence
NM_014425.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INVS | NM_014425.5 | c.2428C>T | p.Arg810Cys | missense_variant | 14/17 | ENST00000262457.7 | |
INVS | NM_001318381.2 | c.2140C>T | p.Arg714Cys | missense_variant | 15/18 | ||
INVS | NM_001318382.2 | c.1450C>T | p.Arg484Cys | missense_variant | 14/17 | ||
INVS | NR_134606.2 | n.2577C>T | non_coding_transcript_exon_variant | 14/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INVS | ENST00000262457.7 | c.2428C>T | p.Arg810Cys | missense_variant | 14/17 | 1 | NM_014425.5 | A2 | |
INVS | ENST00000262456.6 | c.2179+249C>T | intron_variant | 5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249080Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134854
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461874Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4AN XY: 727238
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 810 of the INVS protein (p.Arg810Cys). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with INVS-related conditions. ClinVar contains an entry for this variant (Variation ID: 462713). 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: "Probably 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