9-92332264-T-G

Position:

• chr9-92332264-T-G

Variant summary

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

The NM_001012267.3(CENPP):​c.202T>G​(p.Ser68Ala) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CENPP NM_001012267.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.264

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=0.04348442).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPP	NM_001012267.3	c.202T>G	p.Ser68Ala	missense_variant	2/8	ENST00000375587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPP	ENST00000375587.8	c.202T>G	p.Ser68Ala	missense_variant	2/8	1	NM_001012267.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2024

The c.202T>G (p.S68A) alteration is located in exon 2 (coding exon 2) of the CENPP gene. This alteration results from a T to G substitution at nucleotide position 202, causing the serine (S) at amino acid position 68 to be replaced by an alanine (A). 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	0.071
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.95
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.12	N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.3	N;.
REVEL	Benign	0.039
Sift	Benign	0.25	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;.
Vest4		0.13
MutPred		0.19		Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);
MVP		0.18
MPC		0.15
ClinPred		0.050	T
GERP RS		-0.059
Varity_R		0.067
gMVP		0.093

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: chr9-95094546;