9-135095927-G-A

Variant summary

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

The NM_001282611.2(OLFM1):​c.364G>A​(p.Val122Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,202 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

OLFM1
NM_001282611.2 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.93
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]

Genome browser will be placed here

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
OLFM1NM_001282611.2 linkc.364G>A p.Val122Met missense_variant Exon 3 of 6 ENST00000371793.8 NP_001269540.1 Q99784-1
OLFM1NM_014279.5 linkc.310G>A p.Val104Met missense_variant Exon 3 of 6 NP_055094.1 Q99784-3Q6IMJ8
OLFM1NM_001282612.1 linkc.283G>A p.Val95Met missense_variant Exon 3 of 6 NP_001269541.1 Q99784-5
OLFM1NM_006334.4 linkc.310G>A p.Val104Met missense_variant Exon 3 of 4 NP_006325.1 Q99784-4Q6IMJ7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OLFM1ENST00000371793.8 linkc.364G>A p.Val122Met missense_variant Exon 3 of 6 3 NM_001282611.2 ENSP00000360858.3 Q99784-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
151802
Hom.:
0
Cov.:
30
FAILED QC
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250934
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135694
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
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:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461202
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
726884
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000659
AC:
1
AN:
151802
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
74106
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.310G>A (p.V104M) alteration is located in exon 3 (coding exon 3) of the OLFM1 gene. This alteration results from a G to A substitution at nucleotide position 310, causing the valine (V) at amino acid position 104 to be replaced by a methionine (M). 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
Pathogenic
0.71
BayesDel_addAF
Benign
-0.092
T
BayesDel_noAF
Benign
-0.19
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.038
.;.;T;.;T;.;T;T
Eigen
Pathogenic
0.69
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D;D;D
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.44
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.42
T
MutationAssessor
Uncertain
2.3
.;.;.;.;.;M;M;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-2.0
N;N;N;N;N;N;N;N
REVEL
Benign
0.22
Sift
Uncertain
0.0010
D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D;D;D;D;D
Polyphen
1.0, 0.98
.;.;.;.;.;D;D;.
Vest4
0.56
MutPred
0.42
.;.;.;.;.;Gain of catalytic residue at V122 (P = 0.0877);Gain of catalytic residue at V122 (P = 0.0877);.;
MVP
0.51
MPC
1.1
ClinPred
0.83
D
GERP RS
4.6
Varity_R
0.19
gMVP
0.72

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.

Other links and lift over

dbSNP: rs1205344491; hg19: chr9-137987773; COSMIC: COSV52963450; COSMIC: COSV52963450; API