rs386833860
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004646.4(NPHS1):c.-475_-468del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 145,164 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0042 ( 1 hom., cov: 29)
Consequence
NPHS1
NM_004646.4 5_prime_UTR
NM_004646.4 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.118
Genes affected
NPHS1 (HGNC:7908): (NPHS1 adhesion molecule, nephrin) This gene encodes a member of the immunoglobulin family of cell adhesion molecules that functions in the glomerular filtration barrier in the kidney. The gene is primarily expressed in renal tissues, and the protein is a type-1 transmembrane protein found at the slit diaphragm of glomerular podocytes. The slit diaphragm is thought to function as an ultrafilter to exclude albumin and other plasma macromolecules in the formation of urine. Mutations in this gene result in Finnish-type congenital nephrosis 1, characterized by severe proteinuria and loss of the slit diaphragm and foot processes.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| NPHS1 | NM_004646.4 | c.-475_-468del | 5_prime_UTR_variant | 1/29 | ENST00000378910.10 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NPHS1 | ENST00000378910.10 | c.-475_-468del | 5_prime_UTR_variant | 1/29 | 1 | NM_004646.4 | P2 | ||
| NPHS1 | ENST00000591817.1 | n.560-640_560-633del | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes 0.00418 AC: 607AN: 145086Hom.: 1 Cov.: 29
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.00418 AC: 607AN: 145164Hom.: 1 Cov.: 29 AF XY: 0.00377 AC XY: 266AN XY: 70574
GnomAD4 genome
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29
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Finnish congenital nephrotic syndrome Pathogenic:1Uncertain:1
| Uncertain significance, no assertion criteria provided | curation | Reproductive Health Research and Development, BGI Genomics | Jan 06, 2020 | LRG_693t1:c.-475_-468del has an allele frequency of 0.009 in European (non-Finnish) subpopulation in the gnomAD database. It has been detected in one individual with congenital nephrotic syndrome, known as 489(del(GA)4) (PMID: 9915943). We interpret it as variant of uncertain significance (VUS). ACMG/AMP criteria applied: PP4. - |
| Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at