GeneBe

rs866758642

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198565.3(NRROS):​c.322C>A​(p.Arg108Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R108C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

NRROS
NM_198565.3 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.319

Publications

4 publications found
Variant links:
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_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06775847).

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.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
NRROS
NM_198565.3
MANE Select
c.322C>Ap.Arg108Ser
missense
Exon 3 of 3NP_940967.1Q86YC3

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
NRROS
ENST00000328557.5
TSL:1 MANE Select
c.322C>Ap.Arg108Ser
missense
Exon 3 of 3ENSP00000328625.4Q86YC3
NRROS
ENST00000907983.1
c.322C>Ap.Arg108Ser
missense
Exon 2 of 2ENSP00000578042.1
PIGX
ENST00000426755.5
TSL:3
c.-12+5318C>A
intron
N/AENSP00000409073.1C9JLT7

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
7.8
DANN
Benign
0.97
DEOGEN2
Benign
0.039
T
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.068
T
MetaSVM
Benign
-0.90
T
PhyloP100
-0.32
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-0.91
N
REVEL
Benign
0.10
Sift
Benign
0.17
T
Sift4G
Benign
0.44
T
Polyphen
0.030
B
Vest4
0.11
MutPred
0.46
Loss of helix (P = 0.0558)
MVP
0.13
MPC
0.45
ClinPred
0.12
T
GERP RS
4.3
Varity_R
0.13
gMVP
0.41
Mutation Taster
=93/7
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs866758642; hg19: chr3-196386836; API