Variant 3-196660187-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198565.3(NRROS):c.544C>A(p.Arg182Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,613,064 control chromosomes in the GnomAD database, including 14 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 14 hom. )

Consequence

NRROS
NM_198565.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.10

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008630246).

BP6

Variant 3-196660187-C-A is Benign according to our data. Variant chr3-196660187-C-A is described in ClinVar as [Benign]. Clinvar id is 791024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00159 (242/152344) while in subpopulation AMR AF= 0.00209 (32/15300). AF 95% confidence interval is 0.00152. There are 0 homozygotes in gnomad4. There are 114 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRROS	NM_198565.3 linkuse as main transcript	c.544C>A	p.Arg182Ser	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.544C>A	p.Arg182Ser	missense_variant	3/3	1	NM_198565.3	P1
PIGX	ENST00000426755.5 linkuse as main transcript	c.-12+5540C>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

242

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00229

AC:

570

AN:

249046

Hom.:

AF XY:

0.00234

AC XY:

316

AN XY:

135036

show subpopulations

Gnomad AFR exome

AF:

0.000312

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.0271

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.00156

Gnomad OTH exome

AF:

0.00296

GnomAD4 exome

AF:

0.00221

AC:

3224

AN:

1460720

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

1628

AN XY:

726722

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.0295

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00123

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.00182

Gnomad4 OTH exome

AF:

0.00371

GnomAD4 genome

AF:

0.00159

AC:

242

AN:

152344

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00260

Hom.:

Bravo

AF:

0.00180

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00183

AC:

222

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00240

EpiControl

AF:

0.00196

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.020

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.43

M_CAP

Benign

0.021

MetaRNN

Benign

0.0086

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

0.16

REVEL

Benign

0.027

Sift

Benign

0.14

Sift4G

Benign

0.98

Polyphen

0.0020

Vest4

0.11

MVP

0.28

MPC

0.49

ClinPred

0.0062

GERP RS

3.1

Varity_R

0.12

gMVP

0.46

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