19-9093327-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001004456.2(OR1M1):ā€‹c.83T>Cā€‹(p.Phe28Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,938 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‘“ 0.0000066 ( 0 hom., cov: 30)

Consequence

OR1M1
NM_001004456.2 missense

Scores

3
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43
Variant links:
Genes affected
OR1M1 (HGNC:8220): (olfactory receptor family 1 subfamily M member 1) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR1M1NM_001004456.2 linkc.83T>C p.Phe28Ser missense_variant 2/2 ENST00000641627.1 NP_001004456.1 Q8NGA1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR1M1ENST00000641627.1 linkc.83T>C p.Phe28Ser missense_variant 2/2 NM_001004456.2 ENSP00000493107.1 Q8NGA1
OR1M1ENST00000429566.3 linkc.83T>C p.Phe28Ser missense_variant 1/16 ENSP00000401966.2 Q8NGA1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151938
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000658
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
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151938
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
74180
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000658
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

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 GeneticsJan 26, 2023The c.83T>C (p.F28S) alteration is located in exon 1 (coding exon 1) of the OR1M1 gene. This alteration results from a T to C substitution at nucleotide position 83, causing the phenylalanine (F) at amino acid position 28 to be replaced by a serine (S). 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
0.29
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.081
T;T
Eigen
Benign
-0.050
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.048
.;T
M_CAP
Benign
0.0011
T
MetaRNN
Pathogenic
0.75
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M;M
PrimateAI
Benign
0.26
T
PROVEAN
Pathogenic
-5.2
.;D
REVEL
Benign
0.067
Sift
Pathogenic
0.0
.;D
Sift4G
Uncertain
0.036
.;D
Polyphen
0.99
D;D
Vest4
0.25
MutPred
0.71
Gain of disorder (P = 0.012);Gain of disorder (P = 0.012);
MVP
0.44
MPC
0.13
ClinPred
0.98
D
GERP RS
2.4
Varity_R
0.55
gMVP
0.44

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: rs2050305141; hg19: chr19-9204003; API