1-113980384-G-A

Variant names:

• chr1-113980384-G-A
• rs140666123
• NM_020190.5:c.167G>A

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.167G>A​(p.Arg56Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000414 in 1,447,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R56L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: OLFML3 NM_020190.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73
• 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=0.20626453).

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.167G>A	p.Arg56Gln	missense	Exon 2 of 3	NP_064575.1	M1LAK4
	OLFML3	NM_001286352.3		c.107G>A	p.Arg36Gln	missense	Exon 3 of 4	NP_001273281.1	Q9NRN5-2
	OLFML3	NM_001286353.3		c.-17G>A		5_prime_UTR	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.167G>A	p.Arg56Gln	missense	Exon 2 of 3	ENSP00000322273.4	Q9NRN5-1
	OLFML3	ENST00000854415.1		c.167G>A	p.Arg56Gln	missense	Exon 3 of 4	ENSP00000524474.1
	OLFML3	ENST00000933255.1		c.167G>A	p.Arg56Gln	missense	Exon 2 of 3	ENSP00000603314.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000840 AC: 2 AN: 237972 AF XY: 0.00000783

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000414 AC: 6 AN: 1447718 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718790

African (AFR) AF: 0.00 AC: 0 AN: 33306

American (AMR) AF: 0.00 AC: 0 AN: 43756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24908

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 83062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000543 AC: 6 AN: 1104772

Other (OTH) AF: 0.00 AC: 0 AN: 59886

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.0049	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T
Eigen	Benign	0.021
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.7
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.69	N
REVEL	Uncertain	0.32
Sift	Benign	0.47	T
Sift4G	Benign	0.35	T
Polyphen		0.80	P
Vest4		0.29
MVP		0.79
MPC		0.25
ClinPred		0.58	D
GERP RS		5.4
Varity_R		0.21
gMVP		0.42
Mutation Taster		=89/11	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: rs140666123; hg19: chr1-114523006;