9-92345710-A-C

Variant names:

• chr9-92345710-A-C
• NM_001012267.3:c.390A>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001012267.3(CENPP):​c.390A>C​(p.Arg130Ser) variant causes a missense 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CENPP NM_001012267.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.784

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.017802358).
• BP6: Variant 9-92345710-A-C is Benign according to our data. Variant chr9-92345710-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3490412.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPP	NM_001012267.3	c.390A>C	p.Arg130Ser	missense_variant	Exon 4 of 8	ENST00000375587.8	NP_001012267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPP	ENST00000375587.8	c.390A>C	p.Arg130Ser	missense_variant	Exon 4 of 8	1	NM_001012267.3	ENSP00000364737.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 03, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.5
DANN	Benign	0.78
DEOGEN2	Benign	0.0049	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.00091	T
MetaRNN	Benign	0.018	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.7	N;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.19	N;.
REVEL	Benign	0.030
Sift	Benign	0.79	T;.
Sift4G	Benign	0.58	T;T
Polyphen		0.0010	B;.
Vest4		0.055
MutPred		0.26		Gain of disorder (P = 0.0583);Gain of disorder (P = 0.0583);
MVP		0.081
MPC		0.22
ClinPred		0.044	T
GERP RS		-0.023
Varity_R		0.081
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-95107992;