chr3-196660250-G-A

Position:

chr3-196660250-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_198565.3(NRROS):c.607G>A(p.Gly203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,613,786 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

NRROS
NM_198565.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.400

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]

NRROS links:

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]

PIGX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017034292).

BP6

Variant 3-196660250-G-A is Benign according to our data. Variant chr3-196660250-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3202210.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000355 (54/152296) while in subpopulation AFR AF= 0.00106 (44/41578). AF 95% confidence interval is 0.000809. There are 1 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRROS	NM_198565.3 linkuse as main transcript	c.607G>A	p.Gly203Ser	missense_variant	3/3	ENST00000328557.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRROS	ENST00000328557.5 linkuse as main transcript	c.607G>A	p.Gly203Ser	missense_variant	3/3	1	NM_198565.3	P1
PIGX	ENST00000426755.5 linkuse as main transcript	c.-12+5603G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.0000759

AC:

AN:

250480

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135570

show subpopulations

Gnomad AFR exome

AF:

0.000863

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000541

AC:

AN:

1461490

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.000355

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0000727

Hom.:

Bravo

AF:

0.000457

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.6

DANN

Benign

0.80

DEOGEN2

Benign

0.050

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.57

M_CAP

Benign

0.020

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.2

REVEL

Benign

0.073

Sift

Benign

0.25

Sift4G

Benign

0.11

Polyphen

0.17

Vest4

0.087

MVP

0.18

MPC

0.40

ClinPred

0.016

GERP RS

2.0

Varity_R

0.026

gMVP

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over