1-113980410-C-G

Variant names:

• chr1-113980410-C-G
• rs571776003
• NM_020190.5:c.193C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 15/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

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]

ACMG classification

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=0.11508161).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFML3	NM_020190.5	MANE Select	c.193C>G	p.Leu65Val	missense	Exon 2 of 3	NP_064575.1	M1LAK4
	OLFML3	NM_001286352.3		c.133C>G	p.Leu45Val	missense	Exon 3 of 4	NP_001273281.1	Q9NRN5-2
	OLFML3	NM_001286353.3		c.10C>G	p.Leu4Val	missense	Exon 2 of 3	NP_001273282.1	B4DNG0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFML3	ENST00000320334.5	TSL:1 MANE Select	c.193C>G	p.Leu65Val	missense	Exon 2 of 3	ENSP00000322273.4	Q9NRN5-1
	OLFML3	ENST00000854415.1		c.193C>G	p.Leu65Val	missense	Exon 3 of 4	ENSP00000524474.1
	OLFML3	ENST00000933255.1		c.193C>G	p.Leu65Val	missense	Exon 2 of 3	ENSP00000603314.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32

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: 1 AN: 1459324 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725796

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25920

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110700

Other (OTH) AF: 0.00 AC: 0 AN: 60292

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152238 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74444

African (AFR) AF: 0.00 AC: 0 AN: 41542

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2116

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.0027
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.21
Sift	Benign	0.18	T
Sift4G	Benign	0.32	T
Polyphen		0.46	P
Vest4		0.17
MutPred		0.23		Gain of MoRF binding (P = 0.0972)
MVP		0.61
MPC		0.17
ClinPred		0.52	D
GERP RS		5.2
Varity_R		0.13
gMVP		0.25
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs571776003; hg19: chr1-114523032;