19-35848707-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM5PP3_Moderate
The NM_004646.4(NPHS1):c.1100G>A(p.Arg367His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,132 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R367C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_004646.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHS1 | NM_004646.4 | c.1100G>A | p.Arg367His | missense_variant | 9/29 | ENST00000378910.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHS1 | ENST00000378910.10 | c.1100G>A | p.Arg367His | missense_variant | 9/29 | 1 | NM_004646.4 | P2 | |
NPHS1 | ENST00000353632.6 | c.1100G>A | p.Arg367His | missense_variant | 9/28 | 5 | A2 | ||
NPHS1 | ENST00000592132.1 | n.107G>A | non_coding_transcript_exon_variant | 2/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251338Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135882
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727232
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74434
ClinVar
Submissions by phenotype
Finnish congenital nephrotic syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at