Variant 9-135090252-G-A details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.71

Variant links:

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]

OLFM1 links:

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ACMG classification

Classification made for transcript

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 link	c.208G>A	p.Glu70Lys	missense_variant	Exon 2 of 6	ENST00000371793.8	NP_001269540.1	Q99784-1
OLFM1	NM_014279.5 link	c.154G>A	p.Glu52Lys	missense_variant	Exon 2 of 6		NP_055094.1	Q99784-3Q6IMJ8
OLFM1	NM_001282612.1 link	c.127G>A	p.Glu43Lys	missense_variant	Exon 2 of 6		NP_001269541.1	Q99784-5
OLFM1	NM_006334.4 link	c.154G>A	p.Glu52Lys	missense_variant	Exon 2 of 4		NP_006325.1	Q99784-4Q6IMJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLFM1	ENST00000371793.8 link	c.208G>A	p.Glu70Lys	missense_variant	Exon 2 of 6	3	NM_001282611.2	ENSP00000360858.3		Q99784-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727152

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.054

.;.;T;.;.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D;D;D;D;D

M_CAP

Uncertain

0.19

MetaRNN

Uncertain

0.59

D;D;D;D;D;D

MetaSVM

Uncertain

0.56

MutationAssessor

Benign

1.5

.;.;.;.;L;L

PrimateAI

Pathogenic

0.85

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over