NM_020190.5:c.167G>T

Variant names:

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

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>T​(p.Arg56Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000169 in 1,599,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: OLFML3 NM_020190.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.16020876).

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>T	p.Arg56Leu	missense	Exon 2 of 3	NP_064575.1	M1LAK4
	OLFML3	NM_001286353.3		c.-17G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	NP_001273282.1	B4DNG0
	OLFML3	NM_001286352.3		c.107G>T	p.Arg36Leu	missense	Exon 3 of 4	NP_001273281.1	Q9NRN5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFML3	ENST00000320334.5	TSL:1 MANE Select	c.167G>T	p.Arg56Leu	missense	Exon 2 of 3	ENSP00000322273.4	Q9NRN5-1
	OLFML3	ENST00000393300.6	TSL:3	c.-17G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000376977.3	B4DNG0
	OLFML3	ENST00000854415.1		c.167G>T	p.Arg56Leu	missense	Exon 3 of 4	ENSP00000524474.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152104 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: 0.000386

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

GnomAD2 exomes AF: 0.0000420 AC: 10 AN: 237972 AF XY: 0.0000313

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000492

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000172

GnomAD4 exome AF: 0.0000173 AC: 25 AN: 1447718 Hom.: 0 Cov.: 31 AF XY: 0.0000111 AC XY: 8 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: 0.000176 AC: 7 AN: 39664

South Asian (SAS) AF: 0.0000120 AC: 1 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: 0.00000272 AC: 3 AN: 1104772

Other (OTH) AF: 0.000234 AC: 14 AN: 59886

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152104 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74320

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15274

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

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

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

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	Uncertain	0.47
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	0.061
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.16	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.011	D
Sift4G	Benign	0.071	T
Polyphen		0.39	B
Vest4		0.42
MutPred		0.34		Loss of MoRF binding (P = 0.0291)
MVP		0.74
MPC		0.23
ClinPred		0.17	T
GERP RS		5.4
Varity_R		0.51
gMVP		0.56
Mutation Taster		=72/28	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;