Variant 1-113981294-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020190.5(OLFML3):c.746G>C(p.Arg249Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000758 in 1,451,094 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

OLFML3
NM_020190.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

Variant links:

Genes affected

OLFML3 (HGNC:24956): (olfactomedin like 3) This gene encodes a member of the olfactomedin-like gene family which also includes genes encoding noelin, tiarin, myocilin, amassin, optimedin, photomedin, and latrophilin. The encoded protein is a secreted extracellular matrix glycoprotein with a C-terminal olfactomedin domain that facilitates protein-protein interactions, cell adhesion, and intercellular interactions. It serves as both a scaffold protein that recruits bone morphogenetic protein 1 to its substrate chordin, and as a vascular tissue remodeler with pro-angiogenic properties. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

OLFML3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFML3	NM_020190.5 link	c.746G>C	p.Arg249Pro	missense_variant	3/3	ENST00000320334.5	NP_064575.1
OLFML3	NM_001286352.3 link	c.686G>C	p.Arg229Pro	missense_variant	4/4		NP_001273281.1
OLFML3	NM_001286353.3 link	c.563G>C	p.Arg188Pro	missense_variant	3/3		NP_001273282.1
OLFML3	XM_017001848.3 link	c.686G>C	p.Arg229Pro	missense_variant	3/3		XP_016857337.1	Q9NRN5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFML3	ENST00000320334.5 link	c.746G>C	p.Arg249Pro	missense_variant	3/3	1	NM_020190.5	ENSP00000322273.4		Q9NRN5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000758

AC:

AN:

1451094

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

720604

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000994

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 01, 2023

The c.746G>C (p.R249P) alteration is located in exon 3 (coding exon 3) of the OLFML3 gene. This alteration results from a G to C substitution at nucleotide position 746, causing the arginine (R) at amino acid position 249 to be replaced by a proline (P). 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

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.77

D;.;D

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.068

MetaRNN

Uncertain

0.60

D;D;D

MetaSVM

Uncertain

0.47

MutationAssessor

Uncertain

2.1

.;.;M

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-3.2

.;D;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.018

.;D;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.93, 0.97

.;P;D

Vest4

0.33

MutPred

0.70

.;.;Loss of sheet (P = 0.0457);

MVP

0.90

MPC

0.58

ClinPred

0.95

GERP RS

6.0

Varity_R

0.39

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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