1-113980960-A-C

Position:

• chr1-113980960-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFML3	NM_020190.5	c.412A>C	p.Thr138Pro	missense_variant	3/3	ENST00000320334.5	NP_064575.1
OLFML3	NM_001286352.3	c.352A>C	p.Thr118Pro	missense_variant	4/4		NP_001273281.1
OLFML3	NM_001286353.3	c.229A>C	p.Thr77Pro	missense_variant	3/3		NP_001273282.1
OLFML3	XM_017001848.3	c.352A>C	p.Thr118Pro	missense_variant	3/3		XP_016857337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFML3	ENST00000320334.5	c.412A>C	p.Thr138Pro	missense_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: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.412A>C (p.T138P) alteration is located in exon 3 (coding exon 3) of the OLFML3 gene. This alteration results from a A to C substitution at nucleotide position 412, causing the threonine (T) at amino acid position 138 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.4	.;.;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.3	.;N;N
REVEL	Uncertain	0.61
Sift	Benign	0.051	.;T;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.96, 0.43	.;D;B
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-114523582;