chr19-9854527-C-G

Variant names:

• chr19-9854527-C-G
• rs767544450
• NM_058164.4:c.1024G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_058164.4(OLFM2):​c.1024G>C​(p.Ala342Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A342T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OLFM2 NM_058164.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.81

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OLFM2	NM_058164.4	c.1024G>C	p.Ala342Pro	missense_variant	Exon 6 of 6	ENST00000264833.9	NP_477512.1
OLFM2	NM_001304347.2	c.1096G>C	p.Ala366Pro	missense_variant	Exon 6 of 6		NP_001291276.1
OLFM2	NM_001304348.2	c.790G>C	p.Ala264Pro	missense_variant	Exon 5 of 5		NP_001291277.1
OLFM2	XM_047439713.1	c.820G>C	p.Ala274Pro	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.1024G>C	p.Ala342Pro	missense_variant	Exon 6 of 6	1	NM_058164.4	ENSP00000264833.3
OLFM2	ENST00000593091.2	c.1096G>C	p.Ala366Pro	missense_variant	Exon 6 of 6	5		ENSP00000465809.2
OLFM2	ENST00000590841.5	c.790G>C	p.Ala264Pro	missense_variant	Exon 5 of 5	2		ENSP00000464877.1
OLFM2	ENST00000592448.1	n.*429G>C		downstream_gene_variant		3		ENSP00000466018.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251130 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135792

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461578 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Pathogenic	2.9	M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.1	N;.
REVEL	Pathogenic	0.78
Sift	Uncertain	0.017	D;.
Sift4G	Uncertain	0.027	D;D
Polyphen		1.0	D;.
Vest4		0.73
MutPred		0.53		Loss of sheet (P = 0.0817);.;
MVP		0.45
MPC		2.0
ClinPred		0.94	D
GERP RS		4.4
Varity_R		0.45

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

LitVar

Other links and lift over

dbSNP: rs767544450; hg19: chr19-9965203;