chr19-9854692-C-T

Variant names:

• chr19-9854692-C-T
• rs778414799
• NM_058164.4:c.859G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_058164.4(OLFM2):​c.859G>A​(p.Val287Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: OLFM2 NM_058164.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20762676).

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.859G>A	p.Val287Met	missense	Exon 6 of 6	NP_477512.1	O95897
	OLFM2	NM_001304347.2		c.931G>A	p.Val311Met	missense	Exon 6 of 6	NP_001291276.1	K7EKW2
	OLFM2	NM_001304348.2		c.625G>A	p.Val209Met	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.859G>A	p.Val287Met	missense	Exon 6 of 6	ENSP00000264833.3	O95897
	OLFM2	ENST00000593091.2	TSL:5	c.931G>A	p.Val311Met	missense	Exon 6 of 6	ENSP00000465809.2	K7EKW2
	OLFM2	ENST00000971550.1		c.850G>A	p.Val284Met	missense	Exon 6 of 6	ENSP00000641609.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152248 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251374 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461884 Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74378

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000330 AC: 4

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	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.0074
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.6
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.29
Sift	Benign	0.064	T
Sift4G	Benign	0.12	T
Polyphen		0.64	P
Vest4		0.12
MutPred		0.50		Loss of helix (P = 0.0167)
MVP		0.23
MPC		0.82
ClinPred		0.16	T
GERP RS		4.8
Varity_R		0.085
Mutation Taster		=76/24	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: rs778414799; hg19: chr19-9965368;