rs201738778
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_004646.4(NPHS1):c.3165A>T(p.Ser1055Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,613,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004646.4 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPHS1 | ENST00000378910.10 | c.3165A>T | p.Ser1055Ser | splice_region_variant, synonymous_variant | Exon 23 of 29 | 1 | NM_004646.4 | ENSP00000368190.4 | ||
NPHS1 | ENST00000353632.6 | c.3165A>T | p.Ser1055Ser | splice_region_variant, synonymous_variant | Exon 23 of 28 | 5 | ENSP00000343634.5 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151932Hom.: 0 Cov.: 27
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251470Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135910
GnomAD4 exome AF: 0.000116 AC: 169AN: 1461486Hom.: 0 Cov.: 30 AF XY: 0.0000922 AC XY: 67AN XY: 727054
GnomAD4 genome AF: 0.0000329 AC: 5AN: 151932Hom.: 0 Cov.: 27 AF XY: 0.0000135 AC XY: 1AN XY: 74166
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change affects codon 1055 of the NPHS1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NPHS1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs201738778, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with NPHS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 259495). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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. -
Finnish congenital nephrotic syndrome Uncertain:1
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not specified Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at