19-9854484-T-C

Variant names:

• chr19-9854484-T-C
• NM_058164.4:c.1067A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_058164.4(OLFM2):​c.1067A>G​(p.Glu356Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E356K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OLFM2 NM_058164.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.92

Genes affected

OLFM2 (HGNC:17189): (olfactomedin 2) Involved in positive regulation of smooth muscle cell differentiation. Acts upstream of or within protein secretion. Located in cytoplasm; extracellular region; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
OLFM2	NM_058164.4	c.1067A>G	p.Glu356Gly	missense_variant	Exon 6 of 6	ENST00000264833.9	NP_477512.1
OLFM2	NM_001304347.2	c.1139A>G	p.Glu380Gly	missense_variant	Exon 6 of 6		NP_001291276.1
OLFM2	NM_001304348.2	c.833A>G	p.Glu278Gly	missense_variant	Exon 5 of 5		NP_001291277.1
OLFM2	XM_047439713.1	c.863A>G	p.Glu288Gly	missense_variant	Exon 6 of 6		XP_047295669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLFM2	ENST00000264833.9	c.1067A>G	p.Glu356Gly	missense_variant	Exon 6 of 6	1	NM_058164.4	ENSP00000264833.3
OLFM2	ENST00000593091.2	c.1139A>G	p.Glu380Gly	missense_variant	Exon 6 of 6	5		ENSP00000465809.2
OLFM2	ENST00000590841.5	c.833A>G	p.Glu278Gly	missense_variant	Exon 5 of 5	2		ENSP00000464877.1
OLFM2	ENST00000592448.1	n.*472A>G		downstream_gene_variant		3		ENSP00000466018.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1067A>G (p.E356G) alteration is located in exon 6 (coding exon 6) of the OLFM2 gene. This alteration results from a A to G substitution at nucleotide position 1067, causing the glutamic acid (E) at amino acid position 356 to be replaced by a glycine (G). 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	Benign	0.19
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.5	D;.
REVEL	Pathogenic	0.84
Sift	Uncertain	0.023	D;.
Sift4G	Uncertain	0.017	D;T
Polyphen		0.97	D;.
Vest4		0.49
MutPred		0.59		Gain of catalytic residue at V357 (P = 0.0598);.;
MVP		0.42
MPC		1.7
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.37

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: chr19-9965160;