rs193920761

Variant summary

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

The NM_020190.5(OLFML3):​c.402C>A​(p.Asp134Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000264 in 1,516,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

OLFML3
NM_020190.5 missense, splice_region

Scores

3
16
Splicing: ADA: 0.001656
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.586
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]

Genome browser will be placed here

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=0.23309568).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OLFML3NM_020190.5 linkuse as main transcriptc.402C>A p.Asp134Glu missense_variant, splice_region_variant 3/3 ENST00000320334.5 NP_064575.1
OLFML3NM_001286352.3 linkuse as main transcriptc.342C>A p.Asp114Glu missense_variant, splice_region_variant 4/4 NP_001273281.1
OLFML3NM_001286353.3 linkuse as main transcriptc.219C>A p.Asp73Glu missense_variant, splice_region_variant 3/3 NP_001273282.1
OLFML3XM_017001848.3 linkuse as main transcriptc.342C>A p.Asp114Glu missense_variant, splice_region_variant 3/3 XP_016857337.1 Q9NRN5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OLFML3ENST00000320334.5 linkuse as main transcriptc.402C>A p.Asp134Glu missense_variant, splice_region_variant 3/31 NM_020190.5 ENSP00000322273.4 Q9NRN5-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152246
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00000562
AC:
1
AN:
177808
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
93408
show subpopulations
Gnomad AFR exome
AF:
0.0000657
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000220
AC:
3
AN:
1364002
Hom.:
0
Cov.:
31
AF XY:
0.00000300
AC XY:
2
AN XY:
667714
show subpopulations
Gnomad4 AFR exome
AF:
0.0000663
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.39e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152246
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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
Bravo
AF:
0.0000151
ExAC
AF:
0.00000841
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
T;.;T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.25
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.64
T;T;T
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.23
T;T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
1.0
.;.;L
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.3
.;N;N
REVEL
Benign
0.25
Sift
Benign
0.055
.;T;T
Sift4G
Benign
0.30
T;T;T
Polyphen
0.026, 0.0060
.;B;B
Vest4
0.12
MutPred
0.55
.;.;Gain of MoRF binding (P = 0.1356);
MVP
0.55
MPC
0.16
ClinPred
0.13
T
GERP RS
3.5
Varity_R
0.15
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0017
dbscSNV1_RF
Benign
0.14
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.

Other links and lift over

dbSNP: rs193920761; hg19: chr1-114523572; API