Variant chr3-196660093-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_198565.3(NRROS):c.450C>G(p.Ala150=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 1,612,578 control chromosomes in the GnomAD database, including 472,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43273 hom., cov: 33)

Exomes 𝑓: 0.76 ( 429084 hom. )

Consequence

NRROS
NM_198565.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.206

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 3-196660093-C-G is Benign according to our data. Variant chr3-196660093-C-G is described in ClinVar as [Benign]. Clinvar id is 1326993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.206 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRROS	NM_198565.3 linkuse as main transcript	c.450C>G	p.Ala150=	synonymous_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.450C>G	p.Ala150=	synonymous_variant	3/3	1	NM_198565.3	P1
PIGX	ENST00000426755.5 linkuse as main transcript	c.-12+5446C>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.752

AC:

114349

AN:

152040

Hom.:

43238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.691

Gnomad AMI

AF:

0.742

Gnomad AMR

AF:

0.826

Gnomad ASJ

AF:

0.845

Gnomad EAS

AF:

0.942

Gnomad SAS

AF:

0.838

Gnomad FIN

AF:

0.672

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.758

Gnomad OTH

AF:

0.792

GnomAD3 exomes

AF:

0.789

AC:

196643

AN:

249246

Hom.:

78238

AF XY:

0.789

AC XY:

106592

AN XY:

135068

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.866

Gnomad ASJ exome

AF:

0.844

Gnomad EAS exome

AF:

0.942

Gnomad SAS exome

AF:

0.833

Gnomad FIN exome

AF:

0.679

Gnomad NFE exome

AF:

0.759

Gnomad OTH exome

AF:

0.793

GnomAD4 exome

AF:

0.765

AC:

1117010

AN:

1460420

Hom.:

429084

Cov.:

AF XY:

0.768

AC XY:

557689

AN XY:

726542

show subpopulations

Gnomad4 AFR exome

AF:

0.673

Gnomad4 AMR exome

AF:

0.860

Gnomad4 ASJ exome

AF:

0.845

Gnomad4 EAS exome

AF:

0.950

Gnomad4 SAS exome

AF:

0.830

Gnomad4 FIN exome

AF:

0.685

Gnomad4 NFE exome

AF:

0.753

Gnomad4 OTH exome

AF:

0.780

GnomAD4 genome

AF:

0.752

AC:

114444

AN:

152158

Hom.:

43273

Cov.:

AF XY:

0.755

AC XY:

56146

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.691

Gnomad4 AMR

AF:

0.826

Gnomad4 ASJ

AF:

0.845

Gnomad4 EAS

AF:

0.942

Gnomad4 SAS

AF:

0.839

Gnomad4 FIN

AF:

0.672

Gnomad4 NFE

AF:

0.758

Gnomad4 OTH

AF:

0.793

Alfa

AF:

0.762

Hom.:

14215

Bravo

AF:

0.760

Asia WGS

AF:

0.883

AC:

3070

AN:

3478

EpiCase

AF:

0.763

EpiControl

AF:

0.770

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Seizures, early-onset, with neurodegeneration and brain calcifications

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.9

DANN

Benign

0.77

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