chr9-92325542-T-G

Position:

• chr9-92325542-T-G

Variant summary

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

The NM_001286969.1(CENPP):​c.-611T>G variant causes a 5 prime UTR premature start codon gain 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: CENPP NM_001286969.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPP	NM_001286969.1	c.-611T>G		5_prime_UTR_premature_start_codon_gain_variant	1/7		NP_001273898.1
CENPP	NM_001286969.1	c.-611T>G		5_prime_UTR_variant	1/7		NP_001273898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOL8	ENST00000421075.6	c.-273A>C		5_prime_UTR_variant	1/7	5		ENSP00000390143.2

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

Gnomad4 AFR exome AF: 0.779

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.402

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.288

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

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.385

Alfa AF: 0.339 Hom.: 15186

Bravo AF: 0.419

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.66

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: rs10123342; hg19: chr9-95087824;