rs104895556
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001127255.2(NLRP7):c.346A>T(p.Lys116*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,080 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 not provided (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
NLRP7
NM_001127255.2 stop_gained
NM_001127255.2 stop_gained
Scores
1
2
3
Clinical Significance
Conservation
PhyloP100: 0.383
Publications
1 publications found
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]
NLRP7 Gene-Disease associations (from GenCC):
- hydatidiform mole, recurrent, 1Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- complete hydatidiform moleInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001127255.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NLRP7 | NM_001127255.2 | MANE Select | c.346A>T | p.Lys116* | stop_gained | Exon 3 of 11 | NP_001120727.1 | ||
| NLRP7 | NM_001405531.1 | c.346A>T | p.Lys116* | stop_gained | Exon 5 of 13 | NP_001392460.1 | |||
| NLRP7 | NM_139176.4 | c.346A>T | p.Lys116* | stop_gained | Exon 3 of 11 | NP_631915.2 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NLRP7 | ENST00000592784.6 | TSL:1 MANE Select | c.346A>T | p.Lys116* | stop_gained | Exon 3 of 11 | ENSP00000468706.1 | ||
| NLRP7 | ENST00000588756.5 | TSL:1 | c.346A>T | p.Lys116* | stop_gained | Exon 5 of 13 | ENSP00000467123.1 | ||
| NLRP7 | ENST00000340844.6 | TSL:1 | c.346A>T | p.Lys116* | stop_gained | Exon 3 of 10 | ENSP00000339491.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455080Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 724426 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1455080
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
724426
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33328
American (AMR)
AF:
AC:
0
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26076
East Asian (EAS)
AF:
AC:
0
AN:
39676
South Asian (SAS)
AF:
AC:
1
AN:
86106
European-Finnish (FIN)
AF:
AC:
0
AN:
53408
Middle Eastern (MID)
AF:
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1105884
Other (OTH)
AF:
AC:
0
AN:
60138
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
30
ClinVar
ClinVar submissions as Germline
Significance:not provided
Revision:no classification provided
Pathogenic
VUS
Benign
Condition
-
-
-
Hydatidiform mole, recurrent, 1 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
PhyloP100
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
Splicevardb
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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