9-92325542-T-G

Variant names:

• chr9-92325542-T-G
• rs10123342
• ENST00000358855.8:c.-593A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000421075.6(NOL8):​c.-273A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 154,472 control chromosomes in the GnomAD database, including 14,869 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 0.41 (14739 hom., cov: 32)
  • Exomes 𝑓: 0.28 (130 hom.)
• Consequence: NOL8 ENST00000421075.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585
• Publications: 10 publications found

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]

CENPP (HGNC:32933): (centromere protein P) CENPP is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006 [PubMed 16622420]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000421075.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPP	NM_001286969.1		c.-611T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_001273898.1
	CENPP	NM_001286969.1		c.-611T>G		5_prime_UTR	Exon 1 of 7	NP_001273898.1
	NOL8	NM_017948.6	MANE Select	c.-285A>C		upstream_gene	N/A	NP_060418.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL8	ENST00000358855.8	TSL:1	c.-593A>C		5_prime_UTR	Exon 1 of 18	ENSP00000351723.4
	NOL8	ENST00000421075.6	TSL:5	c.-273A>C		5_prime_UTR	Exon 1 of 7	ENSP00000390143.2
	NOL8	ENST00000545444.5	TSL:5	n.-203A>C		non_coding_transcript_exon	Exon 1 of 15	ENSP00000439829.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61530 AN: 151830 Hom.: 14723 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.284 AC: 716 AN: 2524 Hom.: 130 Cov.: 0 AF XY: 0.273 AC XY: 404 AN XY: 1478

African (AFR) AF: 0.779 AC: 53 AN: 68

American (AMR) AF: 0.284 AC: 21 AN: 74

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 33 AN: 82

East Asian (EAS) AF: 0.208 AC: 15 AN: 72

South Asian (SAS) AF: 0.217 AC: 143 AN: 660

European-Finnish (FIN) AF: 0.202 AC: 17 AN: 84

Middle Eastern (MID) AF: 0.300 AC: 3 AN: 10

European-Non Finnish (NFE) AF: 0.293 AC: 397 AN: 1356

Other (OTH) AF: 0.288 AC: 34 AN: 118

GnomAD4 genome AF: 0.405 AC: 61584 AN: 151948 Hom.: 14739 Cov.: 32 AF XY: 0.396 AC XY: 29414 AN XY: 74278

African (AFR) AF: 0.663 AC: 27469 AN: 41410

American (AMR) AF: 0.290 AC: 4427 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3466

East Asian (EAS) AF: 0.106 AC: 549 AN: 5156

South Asian (SAS) AF: 0.223 AC: 1073 AN: 4820

European-Finnish (FIN) AF: 0.278 AC: 2944 AN: 10578

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.329 AC: 22354 AN: 67944

Other (OTH) AF: 0.385 AC: 808 AN: 2096

Alfa AF: 0.359 Hom.: 29104

Bravo AF: 0.419

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.66
PhyloP100		-0.58
PromoterAI		-0.027	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10123342; hg19: chr9-95087824;