rs77865386

Positions:

• chr3-196661988-A-G
• chr3-196661988-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_198565.3(NRROS):​c.*266A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 329,630 control chromosomes in the GnomAD database, including 36 homozygotes. 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 0.011 (31 hom., cov: 28)
  • Exomes 𝑓: 0.0017 (5 hom.)
• Consequence: NRROS NM_198565.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1546/147198) while in subpopulation AFR AF= 0.0377 (1498/39752). AF 95% confidence interval is 0.0361. There are 31 homozygotes in gnomad4. There are 699 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRROS	NM_198565.3	c.*266A>G		3_prime_UTR_variant	3/3	ENST00000328557.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRROS	ENST00000328557.5	c.*266A>G		3_prime_UTR_variant	3/3	1	NM_198565.3	P1
PIGX	ENST00000426755.5	c.-12+7341A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1541 AN: 147084 Hom.: 31 Cov.: 28

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

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: 0.0000743

Gnomad OTH AF: 0.00543

GnomAD4 exome AF: 0.00168 AC: 307 AN: 182432 Hom.: 5 Cov.: 0 AF XY: 0.00149 AC XY: 139 AN XY: 92982

Gnomad4 AFR exome AF: 0.0425

Gnomad4 AMR exome AF: 0.00248

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000854

Gnomad4 OTH exome AF: 0.00183

GnomAD4 genome AF: 0.0105 AC: 1546 AN: 147198 Hom.: 31 Cov.: 28 AF XY: 0.00976 AC XY: 699 AN XY: 71596

Gnomad4 AFR AF: 0.0377

Gnomad4 AMR AF: 0.00230

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000743

Gnomad4 OTH AF: 0.00538

Alfa AF: 0.00140 Hom.: 0

Bravo AF: 0.0115

Asia WGS AF: 0.00173 AC: 6 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	12
DANN	Benign	0.86

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: rs77865386; hg19: chr3-196388859;