11-7509788-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_198474.4(OLFML1):ā€‹c.809T>Cā€‹(p.Ile270Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000082 ( 0 hom. )

Consequence

OLFML1
NM_198474.4 missense

Scores

9
7
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.97

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OLFML1NM_198474.4 linkuse as main transcriptc.809T>C p.Ile270Thr missense_variant 3/3 ENST00000329293.4 NP_940876.2
LOC124902806XM_047428005.1 linkuse as main transcriptc.*1088-1605A>G intron_variant XP_047283961.1
OLFML1NM_001370498.1 linkuse as main transcriptc.809T>C p.Ile270Thr missense_variant 4/4 NP_001357427.1
OLFML1NM_001370499.1 linkuse as main transcriptc.401T>C p.Ile134Thr missense_variant 3/3 NP_001357428.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OLFML1ENST00000329293.4 linkuse as main transcriptc.809T>C p.Ile270Thr missense_variant 3/31 NM_198474.4 ENSP00000332511 P1
SYT9-AS1ENST00000530201.2 linkuse as main transcriptn.1350+2335A>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152218
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00000795
AC:
2
AN:
251434
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135898
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461882
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152218
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
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:
0.0000151

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 06, 2024The c.809T>C (p.I270T) alteration is located in exon 3 (coding exon 3) of the OLFML1 gene. This alteration results from a T to C substitution at nucleotide position 809, causing the isoleucine (I) at amino acid position 270 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
Benign
0.32
BayesDel_addAF
Pathogenic
0.33
D
BayesDel_noAF
Pathogenic
0.34
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.56
D;D
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.84
.;T
M_CAP
Uncertain
0.18
D
MetaRNN
Pathogenic
0.97
D;D
MetaSVM
Pathogenic
0.89
D
MutationAssessor
Pathogenic
2.9
M;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-4.1
D;D
REVEL
Pathogenic
0.92
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
0.92
P;P
Vest4
0.88
MutPred
0.89
Loss of stability (P = 0.0013);Loss of stability (P = 0.0013);
MVP
0.95
MPC
0.15
ClinPred
0.99
D
GERP RS
5.7
Varity_R
0.66
gMVP
0.78

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: rs1256081414; hg19: chr11-7531019; API