chr9-92390003-C-G

Variant names:

• chr9-92390003-C-G
• rs774564800
• NM_014057.5:c.481G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014057.5(OGN):​c.481G>C​(p.Gly161Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. G161S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: OGN NM_014057.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

Genes affected

OGN (HGNC:8126): (osteoglycin) This gene encodes a member of the small leucine-rich proteoglycan (SLRP) family of proteins. The encoded protein induces ectopic bone formation in conjunction with transforming growth factor beta and may regulate osteoblast differentiation. High expression of the encoded protein may be associated with elevated heart left ventricular mass. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29583305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OGN	NM_014057.5	c.481G>C	p.Gly161Arg	missense_variant	Exon 5 of 7	ENST00000375561.10	NP_054776.1
CENPP	NM_001012267.3	c.564+10144C>G		intron_variant	Intron 5 of 7	ENST00000375587.8	NP_001012267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGN	ENST00000375561.10	c.481G>C	p.Gly161Arg	missense_variant	Exon 5 of 7	1	NM_014057.5	ENSP00000364711.5
CENPP	ENST00000375587.8	c.564+10144C>G		intron_variant	Intron 5 of 7	1	NM_001012267.3	ENSP00000364737.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250620 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135484

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457096 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725188

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;T;.
Eigen	Benign	-0.071
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.6	L;L;.
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.011	D;D;D
Sift4G	Uncertain	0.025	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.47
MutPred		0.52		Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);.;
MVP		0.73
MPC		1.0
ClinPred		0.83	D
GERP RS		1.8
Varity_R		0.20
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs774564800; hg19: chr9-95152285;