NM_004646.4:c.1339G>A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM1BP4_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).
Frequency
Consequence
NM_004646.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPHS1 | ENST00000378910.10 | c.1339G>A | p.Glu447Lys | missense_variant | Exon 11 of 29 | 1 | NM_004646.4 | ENSP00000368190.4 | ||
NPHS1 | ENST00000353632.6 | c.1339G>A | p.Glu447Lys | missense_variant | Exon 11 of 28 | 5 | ENSP00000343634.5 | |||
NPHS1 | ENST00000592132.1 | n.346G>A | non_coding_transcript_exon_variant | Exon 4 of 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
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not provided Benign:2
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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) -
Focal segmental glomerulosclerosis Uncertain:1
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not specified Benign:1
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Proteinuria Benign:1
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Congenital nephrotic syndrome Benign:1
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