chr9-92415238-C-T

Variant names:

• chr9-92415238-C-T
• rs768130443
• NM_005014.3:c.1180G>A

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.1180G>A​(p.Asp394Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: OMD NM_005014.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.596
• Publications: 2 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=0.08019376).

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.1180G>A	p.Asp394Asn	missense	Exon 3 of 3	NP_005005.1	Q99983
	CENPP	NM_001012267.3	MANE Select	c.564+35379C>T		intron	N/A	NP_001012267.1	Q6IPU0-1
	CENPP	NM_001286969.1		c.228+35379C>T		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.1180G>A	p.Asp394Asn	missense	Exon 3 of 3	ENSP00000364700.4	Q99983
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.564+35379C>T		intron	N/A	ENSP00000364737.3	Q6IPU0-1
	OMD	ENST00000949678.1		c.643G>A	p.Asp215Asn	missense	Exon 3 of 3	ENSP00000619737.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251002 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000349 AC: 51 AN: 1461504 Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22 AN XY: 727064

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1111754

Other (OTH) AF: 0.0000331 AC: 2 AN: 60378

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74328

African (AFR) AF: 0.0000483 AC: 2 AN: 41446

American (AMR) AF: 0.000196 AC: 3 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.076
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.60
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.025
Sift	Benign	0.14	T
Sift4G	Benign	0.17	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.21		Gain of catalytic residue at D394 (P = 0.0524)
MVP		0.48
MPC		0.37
ClinPred		0.18	T
GERP RS		1.5
Varity_R		0.035
gMVP		0.26
Mutation Taster		=96/4	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: rs768130443; hg19: chr9-95177520; COSMIC: COSV65020176;