17-3126816-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003555.1(OR1G1):​c.736T>A​(p.Ser246Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,614,090 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S246P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

OR1G1
NM_003555.1 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.663
Variant links:
Genes affected
OR1G1 (HGNC:8204): (olfactory receptor family 1 subfamily G 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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07021451).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR1G1NM_003555.1 linkuse as main transcriptc.736T>A p.Ser246Thr missense_variant 1/1 ENST00000328890.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR1G1ENST00000328890.3 linkuse as main transcriptc.736T>A p.Ser246Thr missense_variant 1/1 NM_003555.1 P1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152206
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0127
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
250798
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135556
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:
0.0000353
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000280
AC:
41
AN:
1461766
Hom.:
0
Cov.:
32
AF XY:
0.0000358
AC XY:
26
AN XY:
727178
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152324
Hom.:
1
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000164
Hom.:
0
Bravo
AF:
0.0000227
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000594

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 GeneticsOct 04, 2022The c.736T>A (p.S246T) alteration is located in exon 1 (coding exon 1) of the OR1G1 gene. This alteration results from a T to A substitution at nucleotide position 736, causing the serine (S) at amino acid position 246 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
0.079
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0036
T
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.60
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.29
T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.070
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.69
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.0080
Sift
Benign
0.35
T
Sift4G
Benign
0.25
T
Polyphen
0.16
B
Vest4
0.073
MutPred
0.38
Loss of disorder (P = 0.1043);
MVP
0.29
MPC
0.28
ClinPred
0.14
T
GERP RS
2.3
Varity_R
0.093
gMVP
0.060

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: rs149783269; hg19: chr17-3030110; COSMIC: COSV61030416; API