9-92321784-T-C

Position:

• chr9-92321784-T-C

Variant summary

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

The NM_017948.6(NOL8):​c.203-38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 990,684 control chromosomes in the GnomAD database, including 1,428 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 0.061 (405 hom., cov: 33)
  • Exomes 𝑓: 0.044 (1023 hom.)
• Consequence: NOL8 NM_017948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

Genes affected

NOL8 (HGNC:23387): (nucleolar protein 8) NOL8 binds Ras-related GTP-binding proteins (see MIM 608267) and plays a role in cell growth (Sekiguchi et al., 2004 [PubMed 14660641]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL8	NM_017948.6	c.203-38A>G		intron_variant		ENST00000442668.7	NP_060418.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOL8	ENST00000442668.7	c.203-38A>G		intron_variant		1	NM_017948.6	ENSP00000401177	P2

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 9316 AN: 152202 Hom.: 406 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.0396

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0417

Gnomad OTH AF: 0.0521

GnomAD3 exomes AF: 0.0471 AC: 4478 AN: 95128 Hom.: 131 AF XY: 0.0474 AC XY: 2466 AN XY: 52076

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.0321

Gnomad ASJ exome AF: 0.0627

Gnomad EAS exome AF: 0.0489

Gnomad SAS exome AF: 0.0667

Gnomad FIN exome AF: 0.0188

Gnomad NFE exome AF: 0.0418

Gnomad OTH exome AF: 0.0402

GnomAD4 exome AF: 0.0439 AC: 36797 AN: 838364 Hom.: 1023 Cov.: 11 AF XY: 0.0449 AC XY: 19344 AN XY: 431062

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.0340

Gnomad4 ASJ exome AF: 0.0639

Gnomad4 EAS exome AF: 0.0488

Gnomad4 SAS exome AF: 0.0696

Gnomad4 FIN exome AF: 0.0203

Gnomad4 NFE exome AF: 0.0404

Gnomad4 OTH exome AF: 0.0473

GnomAD4 genome AF: 0.0612 AC: 9327 AN: 152320 Hom.: 405 Cov.: 33 AF XY: 0.0593 AC XY: 4414 AN XY: 74488

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0399

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.0397

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.0187

Gnomad4 NFE AF: 0.0417

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0504 Hom.: 51

Bravo AF: 0.0645

Asia WGS AF: 0.0900 AC: 314 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.6
DANN	Benign	0.62

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: rs2274967; hg19: chr9-95084066;