9-92415321-C-G

Variant names:

• chr9-92415321-C-G
• rs1207692640
• NM_005014.3:c.1097G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005014.3(OMD):​c.1097G>C​(p.Arg366Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R366Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OMD NM_005014.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 0 publications found

Genes affected

OMD (HGNC:8134): (osteomodulin) Predicted to be involved in cell adhesion and regulation of bone mineralization. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39299548).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005014.3. 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
	OMD	NM_005014.3	MANE Select	c.1097G>C	p.Arg366Pro	missense	Exon 3 of 3	NP_005005.1	Q99983
	CENPP	NM_001012267.3	MANE Select	c.564+35462C>G		intron	N/A	NP_001012267.1	Q6IPU0-1
	CENPP	NM_001286969.1		c.228+35462C>G		intron	N/A	NP_001273898.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OMD	ENST00000375550.5	TSL:1 MANE Select	c.1097G>C	p.Arg366Pro	missense	Exon 3 of 3	ENSP00000364700.4	Q99983
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.564+35462C>G		intron	N/A	ENSP00000364737.3	Q6IPU0-1
	OMD	ENST00000949678.1		c.560G>C	p.Arg187Pro	missense	Exon 3 of 3	ENSP00000619737.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.18
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.028	D
Polyphen		0.95	P
Vest4		0.34
MutPred		0.55		Loss of solvent accessibility (P = 0.1434)
MVP		0.86
MPC		0.50
ClinPred		0.92	D
GERP RS		2.8
Varity_R		0.26
gMVP		0.71
Mutation Taster		=59/41	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

dbSNP: rs1207692640; hg19: chr9-95177603;