9-92337541-G-C

Variant names:

• chr9-92337541-G-C
• NM_001012267.3:c.290G>C

Variant summary

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

The NM_001012267.3(CENPP):​c.290G>C​(p.Ser97Thr) variant causes a missense, splice region 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. 16/24 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CENPP NM_001012267.3 missense, splice_region
• Scores: Splicing: ADA: 0.0009069
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.592

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=0.052508563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPP	NM_001012267.3	c.290G>C	p.Ser97Thr	missense_variant, splice_region_variant	Exon 3 of 8	ENST00000375587.8	NP_001012267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPP	ENST00000375587.8	c.290G>C	p.Ser97Thr	missense_variant, splice_region_variant	Exon 3 of 8	1	NM_001012267.3	ENSP00000364737.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.290G>C (p.S97T) alteration is located in exon 3 (coding exon 3) of the CENPP gene. This alteration results from a G to C substitution at nucleotide position 290, causing the serine (S) at amino acid position 97 to be replaced by a threonine (T). 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	0.099
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.3
DANN	Benign	0.75
DEOGEN2	Benign	0.0062	T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.55	N;.
REVEL	Benign	0.067
Sift	Benign	0.53	T;.
Sift4G	Benign	0.48	T;T
Polyphen		0.42	B;.
Vest4		0.098
MutPred		0.12		Loss of phosphorylation at S97 (P = 0.0503);Loss of phosphorylation at S97 (P = 0.0503);
MVP		0.26
MPC		0.18
ClinPred		0.046	T
GERP RS		-0.93
Varity_R		0.047
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00091
dbscSNV1_RF	Benign	0.18
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.45		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-95099823;