chr19-35846025-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_004646.4(NPHS1):c.1610C>T(p.Thr537Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000632 in 1,585,728 control chromosomes in the GnomAD database, including 8 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. T537T) 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 -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHS1 | NM_004646.4 | c.1610C>T | p.Thr537Met | missense_variant | 12/29 | ENST00000378910.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHS1 | ENST00000378910.10 | c.1610C>T | p.Thr537Met | missense_variant | 12/29 | 1 | NM_004646.4 | P2 | |
NPHS1 | ENST00000353632.6 | c.1610C>T | p.Thr537Met | missense_variant | 12/28 | 5 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000434 AC: 66AN: 152098Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00104 AC: 213AN: 204354Hom.: 2 AF XY: 0.00146 AC XY: 161AN XY: 110436
GnomAD4 exome AF: 0.000654 AC: 937AN: 1433514Hom.: 8 Cov.: 37 AF XY: 0.000861 AC XY: 612AN XY: 710454
GnomAD4 genome AF: 0.000427 AC: 65AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.000497 AC XY: 37AN XY: 74434
ClinVar
Submissions by phenotype
Finnish congenital nephrotic syndrome Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 05, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 10, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
Proteinuria Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Blueprint Genetics | Sep 15, 2014 | - - |
Focal segmental glomerulosclerosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 31, 2020 | - - |
Congenital nephrotic syndrome Uncertain:1
Uncertain significance, 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
NPHS1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 26, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at