Genetic Variant NRROS:c.*266A>T (chr3-196661988-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198565.3(NRROS):c.*266A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000068 in 147,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NRROS
NM_198565.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.49

Publications

1 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]

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRROS	NM_198565.3	MANE Select	c.*266A>T		3_prime_UTR	Exon 3 of 3	NP_940967.1	Q86YC3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRROS	ENST00000328557.5	TSL:1 MANE Select	c.*266A>T	3_prime_UTR	Exon 3 of 3	ENSP00000328625.4	Q86YC3
NRROS	ENST00000907983.1		c.*266A>T	3_prime_UTR	Exon 2 of 2	ENSP00000578042.1
PIGX	ENST00000426755.5	TSL:3	c.-12+7341A>T	intron	N/A	ENSP00000409073.1	C9JLT7

Frequencies

GnomAD3 genomes

AF:

0.00000680

AC:

AN:

147092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

182438

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

92984

African (AFR)

AF:

0.00

AC:

AN:

6032

American (AMR)

AF:

0.00

AC:

AN:

7670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6954

East Asian (EAS)

AF:

0.00

AC:

AN:

15506

South Asian (SAS)

AF:

0.00

AC:

AN:

3750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12460

Middle Eastern (MID)

AF:

0.00

AC:

AN:

938

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

117108

Other (OTH)

AF:

0.00

AC:

AN:

12020

GnomAD4 genome

AF:

0.00000680

AC:

AN:

147092

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39636

American (AMR)

AF:

0.0000720

AC:

AN:

13898

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

4822

South Asian (SAS)

AF:

0.00

AC:

AN:

4610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67266

Other (OTH)

AF:

0.00

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

3.5

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over