chr11-7485916-T-G

Variant summary

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

The NM_198474.4(OLFML1):ā€‹c.41T>Gā€‹(p.Leu14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000079 ( 0 hom., cov: 32)
Exomes š‘“: 0.00014 ( 0 hom. )

Consequence

OLFML1
NM_198474.4 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46
Variant links:
Genes affected
OLFML1 (HGNC:24473): (olfactomedin like 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]
SYT9-AS1 (HGNC:56173): (SYT9 antisense RNA 1)

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/exons MANE UniProt
OLFML1NM_198474.4 linkuse as main transcriptc.41T>G p.Leu14Arg missense_variant 1/3 ENST00000329293.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OLFML1ENST00000329293.4 linkuse as main transcriptc.41T>G p.Leu14Arg missense_variant 1/31 NM_198474.4 P1
SYT9-AS1ENST00000530201.2 linkuse as main transcriptn.1350+26207A>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000836
AC:
21
AN:
251338
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135842
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000185
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000140
AC:
204
AN:
1461738
Hom.:
0
Cov.:
30
AF XY:
0.000129
AC XY:
94
AN XY:
727174
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:
0.000182
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000115
Hom.:
0
Bravo
AF:
0.0000680
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 16, 2023The c.41T>G (p.L14R) alteration is located in exon 1 (coding exon 1) of the OLFML1 gene. This alteration results from a T to G substitution at nucleotide position 41, causing the leucine (L) at amino acid position 14 to be replaced by an arginine (R). 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
Benign
0.17
BayesDel_addAF
Pathogenic
0.16
D
BayesDel_noAF
Pathogenic
0.27
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.011
T;T;.;.
Eigen
Uncertain
0.21
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.64
.;T;T;T
M_CAP
Uncertain
0.095
D
MetaRNN
Uncertain
0.51
D;D;D;D
MetaSVM
Uncertain
0.13
D
MutationAssessor
Uncertain
2.3
M;M;.;.
MutationTaster
Benign
0.88
N;N;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-1.9
N;N;D;D
REVEL
Pathogenic
0.76
Sift
Uncertain
0.0030
D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D
Polyphen
0.94
P;P;.;.
Vest4
0.77
MVP
0.83
MPC
0.090
ClinPred
0.31
T
GERP RS
4.6
Varity_R
0.38
gMVP
0.62

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: rs368217151; hg19: chr11-7507147; API