rs28939695
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1
The NM_004646.4(NPHS1):c.1339G>A(p.Glu447Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00164 in 1,614,068 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E447E) has been classified as Likely benign.
Frequency
Consequence
NM_004646.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHS1 | NM_004646.4 | c.1339G>A | p.Glu447Lys | missense_variant | 11/29 | ENST00000378910.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHS1 | ENST00000378910.10 | c.1339G>A | p.Glu447Lys | missense_variant | 11/29 | 1 | NM_004646.4 | P2 | |
NPHS1 | ENST00000353632.6 | c.1339G>A | p.Glu447Lys | missense_variant | 11/28 | 5 | A2 | ||
NPHS1 | ENST00000592132.1 | n.346G>A | non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00120 AC: 182AN: 152190Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00315 AC: 790AN: 250542Hom.: 21 AF XY: 0.00306 AC XY: 415AN XY: 135694
GnomAD4 exome AF: 0.00169 AC: 2465AN: 1461760Hom.: 58 Cov.: 31 AF XY: 0.00167 AC XY: 1216AN XY: 727182
GnomAD4 genome AF: 0.00119 AC: 182AN: 152308Hom.: 1 Cov.: 32 AF XY: 0.00129 AC XY: 96AN XY: 74490
ClinVar
Submissions by phenotype
Finnish congenital nephrotic syndrome Uncertain:1Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | May 04, 2020 | - - |
Uncertain significance, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Dec 15, 2017 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 15, 2021 | This variant is associated with the following publications: (PMID: 20981092, 27019444, 29259860, 28476686, 29382012, 12631336, 24142548, 10652016, 11317351, 27882743, 26248470, 31216994, 31456999, 31180159, 31308032, 31788464) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Focal segmental glomerulosclerosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Aug 07, 2020 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 26, 2015 | - - |
Proteinuria Benign:1
Likely benign, no assertion criteria provided | clinical testing | Blueprint Genetics | Sep 17, 2014 | - - |
Congenital nephrotic syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at