1-113980366-G-A

Position:

chr1-113980366-G-A

Variant summary

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

The NM_020190.5(OLFML3):c.149G>A(p.Arg50Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000695 in 1,582,082 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R50W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

OLFML3
NM_020190.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.30

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:

OLFML3 (HGNC:):

OLFML3 links:

Genome browser will be placed here

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 linkuse as main transcript	c.149G>A	p.Arg50Gln	missense_variant	2/3	ENST00000320334.5	NP_064575.1
OLFML3	NM_001286352.3 linkuse as main transcript	c.89G>A	p.Arg30Gln	missense_variant	3/4		NP_001273281.1
OLFML3	XM_017001848.3 linkuse as main transcript	c.89G>A	p.Arg30Gln	missense_variant	2/3		XP_016857337.1	Q9NRN5-2
OLFML3	NM_001286353.3 linkuse as main transcript	c.-35G>A		5_prime_UTR_variant	2/3		NP_001273282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OLFML3	ENST00000320334.5 linkuse as main transcript	c.149G>A	p.Arg50Gln	missense_variant	2/3	1	NM_020190.5	ENSP00000322273.4	Q9NRN5-1
OLFML3	ENST00000369551.5 linkuse as main transcript	c.89G>A	p.Arg30Gln	missense_variant	3/4	2		ENSP00000358564.1	Q9NRN5-2
OLFML3	ENST00000393300 linkuse as main transcript	c.-35G>A		5_prime_UTR_variant	2/3	3		ENSP00000376977.3	B4DNG0
OLFML3	ENST00000491700.1 linkuse as main transcript	n.175G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000900

AC:

AN:

222102

Hom.:

AF XY:

0.0000170

AC XY:

AN XY:

117928

show subpopulations

Gnomad AFR exome

AF:

0.0000627

Gnomad AMR exome

AF:

0.00

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:

0.00000997

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000699

AC:

AN:

1429974

Hom.:

Cov.:

AF XY:

0.00000707

AC XY:

AN XY:

707556

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000639

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

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

Aug 19, 2024

The c.149G>A (p.R50Q) alteration is located in exon 2 (coding exon 2) of the OLFML3 gene. This alteration results from a G to A substitution at nucleotide position 149, causing the arginine (R) at amino acid position 50 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.091

.;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.064

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Uncertain

0.22

MutationAssessor

Benign

1.8

.;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.95

N;N

REVEL

Uncertain

0.41

Sift

Benign

0.18

T;T

Sift4G

Benign

0.16

T;T

Polyphen

1.0

D;D

Vest4

0.45

MVP

0.85

MPC

0.36

ClinPred

0.78

GERP RS

5.4

Varity_R

0.20

gMVP

0.48

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