19-9854527-C-T

Variant summary

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

The NM_058164.4(OLFM2):​c.1024G>A​(p.Ala342Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,578 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

OLFM2
NM_058164.4 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.81
Variant links:
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]

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
OLFM2NM_058164.4 linkc.1024G>A p.Ala342Thr missense_variant Exon 6 of 6 ENST00000264833.9 NP_477512.1 O95897
OLFM2NM_001304347.2 linkc.1096G>A p.Ala366Thr missense_variant Exon 6 of 6 NP_001291276.1 O95897K7EKW2
OLFM2NM_001304348.2 linkc.790G>A p.Ala264Thr missense_variant Exon 5 of 5 NP_001291277.1 O95897K7EIS8
OLFM2XM_047439713.1 linkc.820G>A p.Ala274Thr missense_variant Exon 6 of 6 XP_047295669.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OLFM2ENST00000264833.9 linkc.1024G>A p.Ala342Thr missense_variant Exon 6 of 6 1 NM_058164.4 ENSP00000264833.3 O95897
OLFM2ENST00000593091.2 linkc.1096G>A p.Ala366Thr missense_variant Exon 6 of 6 5 ENSP00000465809.2 K7EKW2
OLFM2ENST00000590841.5 linkc.790G>A p.Ala264Thr missense_variant Exon 5 of 5 2 ENSP00000464877.1 K7EIS8
OLFM2ENST00000592448.1 linkn.*429G>A downstream_gene_variant 3 ENSP00000466018.1 K7ELC6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251130
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135792
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
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:
6.84e-7
AC:
1
AN:
1461578
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727106
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
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

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

Submissions by phenotype

not specified Uncertain:1
Sep 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1024G>A (p.A342T) alteration is located in exon 6 (coding exon 6) of the OLFM2 gene. This alteration results from a G to A substitution at nucleotide position 1024, causing the alanine (A) at amino acid position 342 to be replaced by a threonine (T). 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
0.53
BayesDel_addAF
Uncertain
0.034
T
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.22
T;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Uncertain
0.16
D
MetaRNN
Uncertain
0.57
D;D
MetaSVM
Uncertain
0.50
D
MutationAssessor
Benign
1.5
L;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.99
N;.
REVEL
Uncertain
0.55
Sift
Uncertain
0.016
D;.
Sift4G
Uncertain
0.047
D;T
Polyphen
1.0
D;.
Vest4
0.72
MutPred
0.40
Loss of sheet (P = 0.302);.;
MVP
0.35
MPC
1.7
ClinPred
0.92
D
GERP RS
4.4
Varity_R
0.12

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: rs767544450; hg19: chr19-9965203; COSMIC: COSV53431181; COSMIC: COSV53431181; API