NM_001012267.3:c.390A>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 16/21 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
• Publications: 0 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: Likely_benign. The variant received -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 VariationId is 3490412.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012267.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPP	NM_001012267.3	MANE Select	c.390A>C	p.Arg130Ser	missense	Exon 4 of 8	NP_001012267.1	Q6IPU0-1
	CENPP	NM_001286969.1		c.54A>C	p.Arg18Ser	missense	Exon 3 of 7	NP_001273898.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.390A>C	p.Arg130Ser	missense	Exon 4 of 8	ENSP00000364737.3	Q6IPU0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.00091	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.7	N
PhyloP100		-0.78
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.030
Sift	Benign	0.79	T
Sift4G	Benign	0.58	T
Polyphen		0.0010	B
Vest4		0.055
MutPred		0.26		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
Mutation Taster		=99/1	polymorphism

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

hg19: chr9-95107992;