9-92325542-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000358855.8(NOL8):​c.-593A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOL8 ENST00000358855.8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000358855.8. 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>C		5_prime_UTR	Exon 1 of 7	NP_001273898.1
	NOL8	NM_017948.6	MANE Select	c.-285A>G		upstream_gene	N/A	NP_060418.4
	NOL8	NM_001438180.1		c.-411A>G		upstream_gene	N/A	NP_001425109.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2536 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1486

African (AFR) AF: 0.00 AC: 0 AN: 68

American (AMR) AF: 0.00 AC: 0 AN: 74

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 82

East Asian (EAS) AF: 0.00 AC: 0 AN: 72

South Asian (SAS) AF: 0.00 AC: 0 AN: 662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 84

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1366

Other (OTH) AF: 0.00 AC: 0 AN: 118

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.66
PhyloP100		-0.58
PromoterAI		0.035	Neutral

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;