rs866758642

Variant names:

• chr3-196659965-C-A
• rs866758642
• NM_198565.3:c.322C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-196659965-C-A
• chr3-196659965-C-G
• chr3-196659965-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NRROS NM_198565.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRROS	NM_198565.3	c.322C>A	p.Arg108Ser	missense_variant	Exon 3 of 3	ENST00000328557.5	NP_940967.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRROS	ENST00000328557.5	c.322C>A	p.Arg108Ser	missense_variant	Exon 3 of 3	1	NM_198565.3	ENSP00000328625.4
PIGX	ENST00000426755.5	c.-12+5318C>A		intron_variant	Intron 2 of 5	3		ENSP00000409073.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

LitVar

Other links and lift over

dbSNP: rs866758642; hg19: chr3-196386836;