rs2303100

Variant names:

• chr19-9857758-C-A
• NM_058164.4:c.317G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-9857758-C-A
• chr19-9857758-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_058164.4(OLFM2):​c.317G>T​(p.Arg106Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign 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. R106Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OLFM2 NM_058164.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2944405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OLFM2	NM_058164.4	c.317G>T	p.Arg106Leu	missense_variant	Exon 3 of 6	ENST00000264833.9	NP_477512.1
OLFM2	NM_001304347.2	c.389G>T	p.Arg130Leu	missense_variant	Exon 3 of 6		NP_001291276.1
OLFM2	NM_001304348.2	c.83G>T	p.Arg28Leu	missense_variant	Exon 2 of 5		NP_001291277.1
OLFM2	XM_047439713.1	c.113G>T	p.Arg38Leu	missense_variant	Exon 3 of 6		XP_047295669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLFM2	ENST00000264833.9	c.317G>T	p.Arg106Leu	missense_variant	Exon 3 of 6	1	NM_058164.4	ENSP00000264833.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461822 Hom.: 0 Cov.: 61 AF XY: 0.00 AC XY: 0 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;T
Eigen	Benign	-0.0046
Eigen_PC	Benign	0.016
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.5	N;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.0080	D;.;.
Sift4G	Uncertain	0.010	D;D;.
Polyphen		0.75	P;.;.
Vest4		0.39
MutPred		0.38		Loss of methylation at R106 (P = 0.0365);.;.;
MVP		0.068
MPC		1.0
ClinPred		0.81	D
GERP RS		3.9
Varity_R		0.20

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: chr19-9968434;