Genetic Variant OLFML3:p.Arg50Trp (chr1-113980365-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001286353.3(OLFML3):c.-36C>T variant causes a 5 prime UTR premature start codon gain 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_001286353.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.789

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286353.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OLFML3	NM_020190.5	MANE Select	c.148C>T	p.Arg50Trp	missense	Exon 2 of 3	NP_064575.1	M1LAK4
OLFML3	NM_001286353.3		c.-36C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	NP_001273282.1	B4DNG0
OLFML3	NM_001286352.3		c.88C>T	p.Arg30Trp	missense	Exon 3 of 4	NP_001273281.1	Q9NRN5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OLFML3	ENST00000320334.5	TSL:1 MANE Select	c.148C>T	p.Arg50Trp	missense	Exon 2 of 3	ENSP00000322273.4	Q9NRN5-1
OLFML3	ENST00000393300.6	TSL:3	c.-36C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000376977.3	B4DNG0
OLFML3	ENST00000854415.1		c.148C>T	p.Arg50Trp	missense	Exon 3 of 4	ENSP00000524474.1

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

GnomAD2 exomes

AF:

0.0000317

AC:

AN:

220816

AF XY:

0.0000171

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 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

African (AFR)

AF:

0.0000606

AC:

AN:

33010

American (AMR)

AF:

0.000166

AC:

AN:

42278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23354

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39544

South Asian (SAS)

AF:

0.00

AC:

AN:

78840

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5558

European-Non Finnish (NFE)

AF:

0.00000913

AC:

AN:

1095430

Other (OTH)

AF:

0.0000169

AC:

AN:

59108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41538

American (AMR)

AF:

0.000131

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

0.48

MutationAssessor

Benign

1.8

PhyloP100

4.6

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.7

REVEL

Pathogenic

0.65

Sift

Uncertain

0.010

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.69

MVP

0.88

MPC

0.69

ClinPred

0.70

GERP RS

4.4

Varity_R

0.42

gMVP

0.57

Mutation Taster

=77/23

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over