rs372934556
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015102.5(NPHP4):c.3385G>A(p.Val1129Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,662 control chromosomes in the GnomAD database, with no homozygous occurrence. 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_015102.5 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 |
---|---|---|---|---|---|---|---|
NPHP4 | NM_015102.5 | c.3385G>A | p.Val1129Met | missense_variant | 24/30 | ENST00000378156.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHP4 | ENST00000378156.9 | c.3385G>A | p.Val1129Met | missense_variant | 24/30 | 1 | NM_015102.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000223 AC: 34AN: 152152Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000643 AC: 16AN: 248960Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135106
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461392Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 726972
GnomAD4 genome ? AF: 0.000256 AC: 39AN: 152270Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74454
ClinVar
Submissions by phenotype
Senior-Loken syndrome 4;C1847013:Nephronophthisis 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 05, 2022 | - - |
Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1129 of the NPHP4 protein (p.Val1129Met). This variant is present in population databases (rs372934556, gnomAD 0.07%). 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: 289977). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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) | Feb 06, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at