1-113980950-C-G

Position:

• chr1-113980950-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 16/23 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

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 (HGNC:):

ACMG classification

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=0.25902504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFML3	NM_020190.5	c.402C>G	p.Asp134Glu	missense_variant, splice_region_variant	3/3	ENST00000320334.5	NP_064575.1
OLFML3	NM_001286352.3	c.342C>G	p.Asp114Glu	missense_variant, splice_region_variant	4/4		NP_001273281.1
OLFML3	NM_001286353.3	c.219C>G	p.Asp73Glu	missense_variant, splice_region_variant	3/3		NP_001273282.1
OLFML3	XM_017001848.3	c.342C>G	p.Asp114Glu	missense_variant, splice_region_variant	3/3		XP_016857337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFML3	ENST00000320334.5	c.402C>G	p.Asp134Glu	missense_variant, splice_region_variant	3/3	1	NM_020190.5	ENSP00000322273.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.084	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	0.93	D
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.26	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		0.43	T
GERP RS		3.5
Varity_R		0.15
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs193920761; hg19: chr1-114523572; COSMIC: COSV57437251; COSMIC: COSV57437251;