1-113980960-A-C

Variant names:

• chr1-113980960-A-C
• NM_020190.5:c.412A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020190.5(OLFML3):​c.412A>C​(p.Thr138Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OLFML3 NM_020190.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.14
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.412A>C	p.Thr138Pro	missense	Exon 3 of 3	NP_064575.1	M1LAK4
	OLFML3	NM_001286352.3		c.352A>C	p.Thr118Pro	missense	Exon 4 of 4	NP_001273281.1	Q9NRN5-2
	OLFML3	NM_001286353.3		c.229A>C	p.Thr77Pro	missense	Exon 3 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.412A>C	p.Thr138Pro	missense	Exon 3 of 3	ENSP00000322273.4	Q9NRN5-1
	OLFML3	ENST00000854415.1		c.412A>C	p.Thr138Pro	missense	Exon 4 of 4	ENSP00000524474.1
	OLFML3	ENST00000369551.5	TSL:2	c.352A>C	p.Thr118Pro	missense	Exon 4 of 4	ENSP00000358564.1	Q9NRN5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.61
Sift	Benign	0.051	T
Sift4G	Benign	0.25	T
Polyphen		0.96	D
Vest4		0.45
MutPred		0.55		Gain of loop (P = 0.0166)
MVP		0.81
MPC		0.52
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.30
gMVP		0.56
Mutation Taster		=68/32	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

hg19: chr1-114523582;