19-9854204-G-T

Variant names:

• chr19-9854204-G-T
• rs1419683310
• NM_058164.4:c.1347C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 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. 16/21 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037394583).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058164.4. 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
	OLFM2	NM_058164.4	MANE Select	c.1347C>A	p.Ser449Arg	missense	Exon 6 of 6	NP_477512.1	O95897
	OLFM2	NM_001304347.2		c.1419C>A	p.Ser473Arg	missense	Exon 6 of 6	NP_001291276.1	K7EKW2
	OLFM2	NM_001304348.2		c.1113C>A	p.Ser371Arg	missense	Exon 5 of 5	NP_001291277.1	K7EIS8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFM2	ENST00000264833.9	TSL:1 MANE Select	c.1347C>A	p.Ser449Arg	missense	Exon 6 of 6	ENSP00000264833.3	O95897
	OLFM2	ENST00000593091.2	TSL:5	c.1419C>A	p.Ser473Arg	missense	Exon 6 of 6	ENSP00000465809.2	K7EKW2
	OLFM2	ENST00000971550.1		c.1338C>A	p.Ser446Arg	missense	Exon 6 of 6	ENSP00000641609.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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	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
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-1.0	N
PhyloP100		2.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.18
Sift	Benign	0.50	T
Sift4G	Benign	0.46	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
Mutation Taster		=93/7	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: rs1419683310; hg19: chr19-9964880;