rs773368924
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015102.5(NPHP4):c.4145G>A(p.Gly1382Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,605,536 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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. G1382A) has been classified as Likely benign.
Frequency
Consequence
NM_015102.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHP4 | NM_015102.5 | c.4145G>A | p.Gly1382Glu | missense_variant | 30/30 | ENST00000378156.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHP4 | ENST00000378156.9 | c.4145G>A | p.Gly1382Glu | missense_variant | 30/30 | 1 | NM_015102.5 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000464 AC: 7AN: 150792Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000446 AC: 11AN: 246382Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 133858
GnomAD4 exome AF: 0.0000179 AC: 26AN: 1454744Hom.: 1 Cov.: 32 AF XY: 0.00000968 AC XY: 7AN XY: 723244
GnomAD4 genome AF: 0.0000464 AC: 7AN: 150792Hom.: 0 Cov.: 33 AF XY: 0.0000271 AC XY: 2AN XY: 73712
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 23, 2023 | The c.4145G>A (p.G1382E) alteration is located in coding exon 29 of the NPHP4 gene. This alteration results from a G to A substitution at nucleotide position 4145, causing the glycine (G) at amino acid position 1382 to be replaced by a glutamic acid (E). Based on data from gnomAD, the A allele has an overall frequency of 0.005% (13/277688) total alleles studied. The highest observed frequency was 0.062% (12/19528) of East Asian alleles. This amino acid position is not well conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Senior-Loken syndrome 4;C1847013:Nephronophthisis 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1382 of the NPHP4 protein (p.Gly1382Glu). This variant is present in population databases (rs773368924, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. ClinVar contains an entry for this variant (Variation ID: 196631). 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 NPHP4 protein function. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 23, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at