rs7572505

chr2-202287632-G-Achr2-202287632-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015934.5(NOP58):c.435-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,564,552 control chromosomes in the GnomAD database, including 60,469 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 0.34 (10063 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50406 hom.)
• Consequence: NOP58 NM_015934.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

Genes affected

NOP58 (HGNC:29926): (NOP58 ribonucleoprotein) The protein encoded by this gene is a core component of box C/D small nucleolar ribonucleoproteins. Some box C/D small nucleolar RNAs (snoRNAs), such as U3, U8, and U14, are dependent upon the encoded protein for their synthesis. This protein is SUMOylated, which is necessary for high affinity binding to snoRNAs. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOP58	NM_015934.5	c.435-28G>A		intron_variant		ENST00000264279.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOP58	ENST00000264279.10	c.435-28G>A		intron_variant		1	NM_015934.5	P1
NOP58	ENST00000433543.2	c.45-28G>A		intron_variant, NMD_transcript_variant		3
NOP58	ENST00000478941.1	n.459-2691G>A		intron_variant, non_coding_transcript_variant		3
NOP58	ENST00000492688.5	n.341-28G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51049 AN: 151762 Hom.: 10045 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.305

GnomAD3 exomes AF: 0.280 AC: 70081 AN: 250234 Hom.: 11036 AF XY: 0.276 AC XY: 37357 AN XY: 135256

Gnomad AFR exome AF: 0.556

Gnomad AMR exome AF: 0.324

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.130

Gnomad SAS exome AF: 0.358

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.258 AC: 363933 AN: 1412672 Hom.: 50406 Cov.: 23 AF XY: 0.259 AC XY: 182531 AN XY: 705750

Gnomad4 AFR exome AF: 0.552

Gnomad4 AMR exome AF: 0.320

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.0897

Gnomad4 SAS exome AF: 0.356

Gnomad4 FIN exome AF: 0.298

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.337 AC: 51112 AN: 151880 Hom.: 10063 Cov.: 32 AF XY: 0.336 AC XY: 24963 AN XY: 74208

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.302

Alfa AF: 0.241 Hom.: 4880

Bravo AF: 0.345

Asia WGS AF: 0.287 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	11
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7572505; hg19: chr2-203152355; COSMIC: COSV51896762; COSMIC: COSV51896762;