19-9854204-G-T

Position:

• chr19-9854204-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_058164.4(OLFM2):​c.1347C>A​(p.Ser449Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: 2.46

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, OLFM2
• BP4: Computational evidence support a benign effect (MetaRNN=0.037394583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OLFM2	NM_058164.4	c.1347C>A	p.Ser449Arg	missense_variant	6/6	ENST00000264833.9
OLFM2	NM_001304347.2	c.1419C>A	p.Ser473Arg	missense_variant	6/6
OLFM2	NM_001304348.2	c.1113C>A	p.Ser371Arg	missense_variant	5/5
OLFM2	XM_047439713.1	c.1143C>A	p.Ser381Arg	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFM2	ENST00000264833.9	c.1347C>A	p.Ser449Arg	missense_variant	6/6	1	NM_058164.4
OLFM2	ENST00000593091.2	c.1419C>A	p.Ser473Arg	missense_variant	6/6	5		P1
OLFM2	ENST00000590841.5	c.1113C>A	p.Ser371Arg	missense_variant	5/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Apr 07, 2023

The c.1347C>A (p.S449R) alteration is located in exon 6 (coding exon 6) of the OLFM2 gene. This alteration results from a C to A substitution at nucleotide position 1347, causing the serine (S) at amino acid position 449 to be replaced by an arginine (R). 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	0.14
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.73
DEOGEN2	Benign	0.020	T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-1.0	N;.
MutationTaster	Benign	0.85	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.040	N;.
REVEL	Benign	0.18
Sift	Benign	0.50	T;.
Sift4G	Benign	0.46	T;T
Polyphen		0.0	B;.
Vest4		0.083
MutPred		0.30		Loss of glycosylation at S449 (P = 0.0046);.;
MVP		0.068
MPC		0.79
ClinPred		0.18	T
GERP RS		3.3
Varity_R		0.073

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: chr19-9964880;