Genetic Variant OLFML3:p.Asp134Glu (chr1-113980950-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020190.5(OLFML3):c.402C>G(p.Asp134Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

OLFML3
NM_020190.5 missense, splice_region

Scores

Splicing: ADA: 0.001022

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.586

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25902504).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020190.5. 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.402C>G	p.Asp134Glu	missense splice_region	Exon 3 of 3	NP_064575.1	M1LAK4
OLFML3	NM_001286352.3		c.342C>G	p.Asp114Glu	missense splice_region	Exon 4 of 4	NP_001273281.1	Q9NRN5-2
OLFML3	NM_001286353.3		c.219C>G	p.Asp73Glu	missense splice_region	Exon 3 of 3	NP_001273282.1	B4DNG0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OLFML3	ENST00000320334.5	TSL:1 MANE Select	c.402C>G	p.Asp134Glu	missense splice_region	Exon 3 of 3	ENSP00000322273.4	Q9NRN5-1
OLFML3	ENST00000854415.1		c.402C>G	p.Asp134Glu	missense splice_region	Exon 4 of 4	ENSP00000524474.1
OLFML3	ENST00000369551.5	TSL:2	c.342C>G	p.Asp114Glu	missense splice_region	Exon 4 of 4	ENSP00000358564.1	Q9NRN5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.64

M_CAP

Benign

0.038

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.0

PhyloP100

0.59

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.3

REVEL

Benign

0.25

Sift

Benign

0.055

Sift4G

Benign

0.30

Polyphen

0.026

Vest4

0.12

MutPred

0.55

Gain of MoRF binding (P = 0.1356)

MVP

0.55

MPC

0.16

ClinPred

0.43

GERP RS

3.5

Varity_R

0.15

gMVP

0.43

Mutation Taster

=45/55

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0010

dbscSNV1_RF

Benign

0.13

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over