Variant 1-113980365-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020190.5(OLFML3):c.148C>T(p.Arg50Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000202 in 1,581,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

OLFML3
NM_020190.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.789

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OLFML3	NM_020190.5 linkuse as main transcript	c.148C>T	p.Arg50Trp	missense_variant	2/3	ENST00000320334.5
OLFML3	NM_001286352.3 linkuse as main transcript	c.88C>T	p.Arg30Trp	missense_variant	3/4
OLFML3	XM_017001848.3 linkuse as main transcript	c.88C>T	p.Arg30Trp	missense_variant	2/3
OLFML3	NM_001286353.3 linkuse as main transcript	c.-36C>T		5_prime_UTR_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFML3	ENST00000320334.5 linkuse as main transcript	c.148C>T	p.Arg50Trp	missense_variant	2/3	1	NM_020190.5	P1	Q9NRN5-1
OLFML3	ENST00000369551.5 linkuse as main transcript	c.88C>T	p.Arg30Trp	missense_variant	3/4	2			Q9NRN5-2
OLFML3	ENST00000393300.6 linkuse as main transcript	c.-36C>T		5_prime_UTR_variant	2/3	3
OLFML3	ENST00000491700.1 linkuse as main transcript	n.174C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000317

AC:

AN:

220816

Hom.:

AF XY:

0.0000171

AC XY:

AN XY:

117152

show subpopulations

Gnomad AFR exome

AF:

0.000189

Gnomad AMR exome

AF:

0.0000934

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:

0.00

Gnomad OTH exome

AF:

0.000185

GnomAD4 exome

AF:

0.0000147

AC:

AN:

1428970

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

706964

show subpopulations

Gnomad4 AFR exome

AF:

0.0000606

Gnomad4 AMR exome

AF:

0.000166

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000913

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000453

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

Mar 18, 2024

The c.148C>T (p.R50W) alteration is located in exon 2 (coding exon 2) of the OLFML3 gene. This alteration results from a C to T substitution at nucleotide position 148, causing the arginine (R) at amino acid position 50 to be replaced by a tryptophan (W). 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

Uncertain

0.35

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.93

D;D

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Uncertain

0.48

MutationAssessor

Benign

1.8

.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.7

D;D

REVEL

Pathogenic

0.65

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

1.0

D;D

Vest4

0.69

MVP

0.88

MPC

0.69

ClinPred

0.70

GERP RS

4.4

Varity_R

0.42

gMVP

0.57

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