9-92585202-A-C

Variant names:

• chr9-92585202-A-C
• rs10491805
• NM_001012267.3:c.565-26112A>C

Variant summary

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

The NM_001012267.3(CENPP):​c.565-26112A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 152,330 control chromosomes in the GnomAD database, including 333 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 0.027 (333 hom., cov: 32)
• Consequence: CENPP NM_001012267.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512
• Publications: 1 publications found

Genes affected

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPP	NM_001012267.3	c.565-26112A>C		intron_variant	Intron 5 of 7	ENST00000375587.8	NP_001012267.1
CENPP	NM_001286969.1	c.229-26112A>C		intron_variant	Intron 4 of 6		NP_001273898.1
CENPP	XM_024447543.2	c.289-26112A>C		intron_variant	Intron 5 of 7		XP_024303311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPP	ENST00000375587.8	c.565-26112A>C		intron_variant	Intron 5 of 7	1	NM_001012267.3	ENSP00000364737.3

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4073 AN: 152212 Hom.: 329 Cov.: 32

Gnomad AFR AF: 0.00639

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.00868

Gnomad FIN AF: 0.0307

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00397

Gnomad OTH AF: 0.0263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0268 AC: 4081 AN: 152330 Hom.: 333 Cov.: 32 AF XY: 0.0307 AC XY: 2288 AN XY: 74486

African (AFR) AF: 0.00637 AC: 265 AN: 41590

American (AMR) AF: 0.160 AC: 2446 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.130 AC: 676 AN: 5184

South Asian (SAS) AF: 0.00869 AC: 42 AN: 4834

European-Finnish (FIN) AF: 0.0307 AC: 326 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00397 AC: 270 AN: 68020

Other (OTH) AF: 0.0255 AC: 54 AN: 2116

Alfa AF: 0.0228 Hom.: 196

Bravo AF: 0.0383

Asia WGS AF: 0.0610 AC: 213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.71
PhyloP100		-0.51
Mutation Taster		=100/0	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: rs10491805; hg19: chr9-95347484;