rs778043242
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_015102.5(NPHP4):c.1462C>T(p.Arg488*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000048 in 1,604,058 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). 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 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NPHP4 | NM_015102.5 | c.1462C>T | p.Arg488* | stop_gained | Exon 12 of 30 | ENST00000378156.9 | NP_055917.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPHP4 | ENST00000378156.9 | c.1462C>T | p.Arg488* | stop_gained | Exon 12 of 30 | 1 | NM_015102.5 | ENSP00000367398.4 | ||
NPHP4 | ENST00000489180.6 | n.1462C>T | non_coding_transcript_exon_variant | Exon 12 of 33 | 2 | ENSP00000423747.1 | ||||
NPHP4 | ENST00000378169.7 | n.*516-3413C>T | intron_variant | Intron 10 of 26 | 1 | ENSP00000367411.3 |
Frequencies
GnomAD3 genomes AF: 0.0000855 AC: 13AN: 152124Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000609 AC: 14AN: 230052Hom.: 1 AF XY: 0.0000802 AC XY: 10AN XY: 124644
GnomAD4 exome AF: 0.0000441 AC: 64AN: 1451934Hom.: 1 Cov.: 32 AF XY: 0.0000402 AC XY: 29AN XY: 720942
GnomAD4 genome AF: 0.0000855 AC: 13AN: 152124Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74310
ClinVar
Submissions by phenotype
Nephronophthisis Pathogenic:1
This sequence change creates a premature translational stop signal (p.Arg488*) 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). This variant is present in population databases (rs778043242, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individual(s) with nephronophthisis (PMID: 15776426). ClinVar contains an entry for this variant (Variation ID: 297820). For these reasons, this variant has been classified as Pathogenic. -
Nephronophthisis 4 Pathogenic:1
PVS1,PM2_p,PM3 -
not provided Uncertain:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at