2-110123865-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001128178.3(NPHP1):c.1960G>A(p.Gly654Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,614,054 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001128178.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHP1 | NM_001128178.3 | c.1960G>A | p.Gly654Arg | missense_variant | 20/20 | ENST00000445609.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHP1 | ENST00000445609.7 | c.1960G>A | p.Gly654Arg | missense_variant | 20/20 | 1 | NM_001128178.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152108Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251486Hom.: 1 AF XY: 0.0000515 AC XY: 7AN XY: 135918
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461828Hom.: 1 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727224
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74436
ClinVar
Submissions by phenotype
Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 06, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 710 of the NPHP1 protein (p.Gly710Arg). This variant is present in population databases (rs781531545, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with NPHP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1429265). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Joubert syndrome with renal defect;C1855681:Nephronophthisis 1;C4551559:Senior-Loken syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 15, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at