1-5863314-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015102.5(NPHP4):āc.4232A>Gā(p.His1411Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. H1411H) has been classified as Likely benign.
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NPHP4 | NM_015102.5 | c.4232A>G | p.His1411Arg | missense_variant | 30/30 | ENST00000378156.9 | NP_055917.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPHP4 | ENST00000378156.9 | c.4232A>G | p.His1411Arg | missense_variant | 30/30 | 1 | NM_015102.5 | ENSP00000367398.4 | ||
NPHP4 | ENST00000378169.7 | n.*3133A>G | non_coding_transcript_exon_variant | 27/27 | 1 | ENSP00000367411.3 | ||||
NPHP4 | ENST00000489180.6 | n.*2043A>G | non_coding_transcript_exon_variant | 33/33 | 2 | ENSP00000423747.1 | ||||
NPHP4 | ENST00000378169.7 | n.*3133A>G | 3_prime_UTR_variant | 27/27 | 1 | ENSP00000367411.3 | ||||
NPHP4 | ENST00000489180.6 | n.*2043A>G | 3_prime_UTR_variant | 33/33 | 2 | ENSP00000423747.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000809 AC: 2AN: 247138Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134280
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461684Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727124
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74374
ClinVar
Submissions by phenotype
Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 30, 2021 | This sequence change replaces histidine with arginine at codon 1411 of the NPHP4 protein (p.His1411Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs762068143, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at