9-92415190-C-A

Variant names:

• chr9-92415190-C-A
• rs189375297
• NM_005014.3:c.1228G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005014.3(OMD):​c.1228G>T​(p.Gly410Trp) 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. 15/22 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. G410R) 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: 1.35
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19601038).

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.1228G>T	p.Gly410Trp	missense	Exon 3 of 3	NP_005005.1	Q99983
	CENPP	NM_001012267.3	MANE Select	c.564+35331C>A		intron	N/A	NP_001012267.1	Q6IPU0-1
	CENPP	NM_001286969.1		c.228+35331C>A		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.1228G>T	p.Gly410Trp	missense	Exon 3 of 3	ENSP00000364700.4	Q99983
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.564+35331C>A		intron	N/A	ENSP00000364737.3	Q6IPU0-1
	OMD	ENST00000949678.1		c.691G>T	p.Gly231Trp	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	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.044
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.011	D
Polyphen		0.93	P
Vest4		0.23
MutPred		0.34		Gain of sheet (P = 0.1208)
MVP		0.45
MPC		0.45
ClinPred		0.80	D
GERP RS		5.4
Varity_R		0.097
gMVP		0.21
Mutation Taster		=86/14	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: rs189375297; hg19: chr9-95177472;