9-135090252-G-A

Variant names:

• chr9-135090252-G-A
• rs1282340447
• NM_001282611.2:c.208G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001282611.2(OLFM1):​c.208G>A​(p.Glu70Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OLFM1 NM_001282611.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.71

Genes affected

OLFM1 (HGNC:17187): (olfactomedin 1) This gene product shares extensive sequence similarity with the rat neuronal olfactomedin-related ER localized protein. While the exact function of the encoded protein is not known, its abundant expression in brain suggests that it may have an essential role in nerve tissue. Several alternatively spliced transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OLFM1	NM_001282611.2	c.208G>A	p.Glu70Lys	missense_variant	Exon 2 of 6	ENST00000371793.8	NP_001269540.1
OLFM1	NM_014279.5	c.154G>A	p.Glu52Lys	missense_variant	Exon 2 of 6		NP_055094.1
OLFM1	NM_001282612.1	c.127G>A	p.Glu43Lys	missense_variant	Exon 2 of 6		NP_001269541.1
OLFM1	NM_006334.4	c.154G>A	p.Glu52Lys	missense_variant	Exon 2 of 4		NP_006325.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLFM1	ENST00000371793.8	c.208G>A	p.Glu70Lys	missense_variant	Exon 2 of 6	3	NM_001282611.2	ENSP00000360858.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461724 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.154G>A (p.E52K) alteration is located in exon 2 (coding exon 2) of the OLFM1 gene. This alteration results from a G to A substitution at nucleotide position 154, causing the glutamic acid (E) at amino acid position 52 to be replaced by a lysine (K). 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	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.054	.;.;T;.;.;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.59	D;D;D;D;D;D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Benign	1.5	.;.;.;.;L;L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.2	N;N;N;N;N;N
REVEL	Uncertain	0.51
Sift	Uncertain	0.0060	D;D;D;D;D;D
Sift4G	Uncertain	0.029	D;D;D;D;D;D
Polyphen		0.97, 0.97	.;.;.;.;D;D
Vest4		0.58
MutPred		0.48		.;.;.;.;Gain of ubiquitination at E70 (P = 0.0128);Gain of ubiquitination at E70 (P = 0.0128);
MVP		0.70
MPC		2.0
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.30
gMVP		0.61

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: rs1282340447; hg19: chr9-137982098;