Variant chr9-92415300-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005014.3(OMD):c.1118T>C(p.Ile373Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,490 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

OMD
NM_005014.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.89

Variant links:

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]

OMD links:

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]

CENPP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1678848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OMD	NM_005014.3 linkuse as main transcript	c.1118T>C	p.Ile373Thr	missense_variant	3/3	ENST00000375550.5	NP_005005.1	Q99983
CENPP	NM_001012267.3 linkuse as main transcript	c.564+35441A>G		intron_variant		ENST00000375587.8	NP_001012267.1	Q6IPU0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OMD	ENST00000375550.5 linkuse as main transcript	c.1118T>C	p.Ile373Thr	missense_variant	3/3	1	NM_005014.3	ENSP00000364700.4		Q99983
CENPP	ENST00000375587.8 linkuse as main transcript	c.564+35441A>G		intron_variant		1	NM_001012267.3	ENSP00000364737.3		Q6IPU0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250942

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135646

show subpopulations

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461490

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2024

The c.1118T>C (p.I373T) alteration is located in exon 3 (coding exon 2) of the OMD gene. This alteration results from a T to C substitution at nucleotide position 1118, causing the isoleucine (I) at amino acid position 373 to be replaced by a threonine (T). 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

0.16

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.17

Eigen

Benign

-0.073

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.65

M_CAP

Benign

0.0067

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.010

REVEL

Benign

0.12

Sift

Benign

0.50

Sift4G

Benign

0.62

Polyphen

0.010

Vest4

0.045

MutPred

0.65

Gain of disorder (P = 0.0273);

MVP

0.71

MPC

0.18

ClinPred

0.20

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.064

gMVP

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over