rs762737130
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_198565.3(NRROS):c.190delC(p.Leu64TrpfsTer81) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
NRROS
NM_198565.3 frameshift
NM_198565.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.75
Publications
1 publications found
Genes affected
NRROS (HGNC:24613): (negative regulator of reactive oxygen species) Enables transforming growth factor beta binding activity. Predicted to be involved in several processes, including microglia development; sequestering of TGFbeta in extracellular matrix; and transforming growth factor beta1 activation. Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]
PIGX (HGNC:26046): (phosphatidylinositol glycan anchor biosynthesis class X) This gene encodes a type I transmembrane protein in the endoplasmic reticulum (ER). The protein is an essential component of glycosylphosphatidylinositol-mannosyltransferase I, which transfers the first of the four mannoses in the GPI-anchor precursors during GPI-anchor biosynthesis. Studies in rat indicate that the protein is translated from a non-AUG translation initiation site. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 10 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-196659830-AC-A is Pathogenic according to our data. Variant chr3-196659830-AC-A is described in ClinVar as Pathogenic. ClinVar VariationId is 873032.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_198565.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NRROS | NM_198565.3 | MANE Select | c.190delC | p.Leu64TrpfsTer81 | frameshift | Exon 3 of 3 | NP_940967.1 | Q86YC3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NRROS | ENST00000328557.5 | TSL:1 MANE Select | c.190delC | p.Leu64TrpfsTer81 | frameshift | Exon 3 of 3 | ENSP00000328625.4 | Q86YC3 | |
| NRROS | ENST00000907983.1 | c.190delC | p.Leu64TrpfsTer81 | frameshift | Exon 2 of 2 | ENSP00000578042.1 | |||
| PIGX | ENST00000426755.5 | TSL:3 | c.-12+5186delC | intron | N/A | ENSP00000409073.1 | C9JLT7 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251156 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251156
AF XY:
Gnomad AFR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461794Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4AN XY: 727214 show subpopulations
GnomAD4 exome
AF:
AC:
6
AN:
1461794
Hom.:
Cov.:
30
AF XY:
AC XY:
4
AN XY:
727214
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26128
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53410
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
6
AN:
1111948
Other (OTH)
AF:
AC:
0
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.517
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
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GnomAD4 genome
GnomAD4 genome
Cov.:
31
Alfa
AF:
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ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Seizures, early-onset, with neurodegeneration and brain calcifications (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
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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