9-92326099-G-A

Variant names:

• chr9-92326099-G-A
• rs750852584
• NM_001012267.3:c.101G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001012267.3(CENPP):​c.101G>A​(p.Arg34Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,395,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: CENPP NM_001012267.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.38

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04155004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPP	NM_001012267.3	c.101G>A	p.Arg34Gln	missense_variant	Exon 1 of 8	ENST00000375587.8	NP_001012267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPP	ENST00000375587.8	c.101G>A	p.Arg34Gln	missense_variant	Exon 1 of 8	1	NM_001012267.3	ENSP00000364737.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000640 AC: 1 AN: 156314 Hom.: 0 AF XY: 0.0000120 AC XY: 1 AN XY: 83538

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000402

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000287 AC: 4 AN: 1395246 Hom.: 0 Cov.: 30 AF XY: 0.00000436 AC XY: 3 AN XY: 687712

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000826

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.101G>A (p.R34Q) alteration is located in exon 1 (coding exon 1) of the CENPP gene. This alteration results from a G to A substitution at nucleotide position 101, causing the arginine (R) at amino acid position 34 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.2
DANN	Benign	0.97
DEOGEN2	Benign	0.0065	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.40	T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.14	N;.
REVEL	Benign	0.015
Sift	Benign	0.41	T;.
Sift4G	Benign	0.55	T;T
Polyphen		0.010	B;.
Vest4		0.020
MutPred		0.30		Loss of MoRF binding (P = 0.0377);Loss of MoRF binding (P = 0.0377);
MVP		0.15
MPC		0.26
ClinPred		0.039	T
GERP RS		-5.7
Varity_R		0.045
gMVP		0.14

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: rs750852584; hg19: chr9-95088381;