Variant chr1-113980410-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020190.5(OLFML3):c.193C>G(p.Leu65Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,611,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

OLFML3
NM_020190.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11508161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OLFML3	NM_020190.5 linkuse as main transcript	c.193C>G	p.Leu65Val	missense_variant	2/3	ENST00000320334.5
OLFML3	NM_001286352.3 linkuse as main transcript	c.133C>G	p.Leu45Val	missense_variant	3/4
OLFML3	NM_001286353.3 linkuse as main transcript	c.10C>G	p.Leu4Val	missense_variant	2/3
OLFML3	XM_017001848.3 linkuse as main transcript	c.133C>G	p.Leu45Val	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFML3	ENST00000320334.5 linkuse as main transcript	c.193C>G	p.Leu65Val	missense_variant	2/3	1	NM_020190.5	P1	Q9NRN5-1
OLFML3	ENST00000369551.5 linkuse as main transcript	c.133C>G	p.Leu45Val	missense_variant	3/4	2			Q9NRN5-2
OLFML3	ENST00000393300.6 linkuse as main transcript	c.10C>G	p.Leu4Val	missense_variant	2/3	3
OLFML3	ENST00000491700.1 linkuse as main transcript	n.219C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459324

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725796

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Jan 27, 2022

The c.193C>G (p.L65V) alteration is located in exon 2 (coding exon 2) of the OLFML3 gene. This alteration results from a C to G substitution at nucleotide position 193, causing the leucine (L) at amino acid position 65 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

T;.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

0.0027

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.4

.;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.98

.;N;N

REVEL

Benign

0.21

Sift

Benign

0.18

.;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.46, 0.16

.;P;B

Vest4

0.17

MutPred

0.23

.;.;Gain of MoRF binding (P = 0.0972);

MVP

0.61

MPC

0.17

ClinPred

0.52

GERP RS

5.2

Varity_R

0.13

gMVP

0.25

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