rs137852923
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015102.5(NPHP4):c.1972C>T(p.Arg658Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_015102.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHP4 | NM_015102.5 | c.1972C>T | p.Arg658Ter | stop_gained | 16/30 | ENST00000378156.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHP4 | ENST00000378156.9 | c.1972C>T | p.Arg658Ter | stop_gained | 16/30 | 1 | NM_015102.5 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249268Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135232
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461682Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727122
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Nephronophthisis Pathogenic:1Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 25, 2021 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 3405). This premature translational stop signal has been observed in individual(s) with nephronophthisis (PMID: 12205563). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs137852923, ExAC 0.006%). This sequence change creates a premature translational stop signal (p.Arg658*) in the NPHP4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPHP4 are known to be pathogenic (PMID: 12205563, 23559409). - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Senior-Loken syndrome 4 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2002 | - - |
Nephronophthisis 4 Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare | Aug 16, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at