rs104895547
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_001405531.1(NLRP7):c.952_953insGCAGCAGCCGATCT(p.Tyr318CysfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 152,124 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: đť‘“ 0.000066 ( 0 hom., cov: 32)
Exomes đť‘“: 0.00010 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NLRP7
NM_001405531.1 frameshift
NM_001405531.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.238
Genes affected
NLRP7 (HGNC:22947): (NLR family pyrin domain containing 7) This gene encodes a member of the NACHT, leucine rich repeat, and PYD containing (NLRP) protein family. It has an N-terminal pyrin domain, followed by a NACHT domain, a NACHT-associated domain (NAD), and a C-terminal leucine-rich repeat (LRR) region. NLRP proteins are implicated in the activation of proinflammatory caspases through multiprotein complexes called inflammasomes. This gene may act as a feedback regulator of caspase-1-dependent interleukin 1-beta secretion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 19-54939866-T-TAGATCGGCTGCTGC is Pathogenic according to our data. Variant chr19-54939866-T-TAGATCGGCTGCTGC is described in ClinVar as [Pathogenic]. Clinvar id is 97807.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NLRP7 | NM_001127255.2 | c.952_953insGCAGCAGCCGATCT | p.Tyr318CysfsTer7 | frameshift_variant | 4/11 | ENST00000592784.6 | |
NLRP7 | NM_001405531.1 | c.952_953insGCAGCAGCCGATCT | p.Tyr318CysfsTer7 | frameshift_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NLRP7 | ENST00000592784.6 | c.952_953insGCAGCAGCCGATCT | p.Tyr318CysfsTer7 | frameshift_variant | 4/11 | 1 | NM_001127255.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152124Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251372Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135886
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000999 AC: 146AN: 1461786Hom.: 0 Cov.: 39 AF XY: 0.0000949 AC XY: 69AN XY: 727182
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74308
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hydatidiform mole, recurrent, 1 Pathogenic:1Other:1
not provided, no classification provided | literature only | Unité médicale des maladies autoinflammatoires, CHRU Montpellier | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2013 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at