19-14881234-C-T

Variant summary

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

The NM_030901.2(OR7A17):​c.122G>A​(p.Gly41Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,792 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G41R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

OR7A17
NM_030901.2 missense

Scores

3
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.184
Variant links:
Genes affected
OR7A17 (HGNC:8363): (olfactory receptor family 7 subfamily A member 17) 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, 0.789

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR7A17NM_030901.2 linkc.122G>A p.Gly41Glu missense_variant Exon 3 of 3 ENST00000641113.1 NP_112163.1 O14581A0A126GVR5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR7A17ENST00000641113.1 linkc.122G>A p.Gly41Glu missense_variant Exon 3 of 3 NM_030901.2 ENSP00000493283.1 O14581
OR7A17ENST00000642123.1 linkc.122G>A p.Gly41Glu missense_variant Exon 3 of 3 ENSP00000493071.1 O14581

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151946
Hom.:
0
Cov.:
31
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:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461846
Hom.:
0
Cov.:
35
AF XY:
0.00000275
AC XY:
2
AN XY:
727216
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151946
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74214
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:
0.00
Gnomad4 OTH
AF:
0.000478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 15, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.122G>A (p.G41E) alteration is located in exon 1 (coding exon 1) of the OR7A17 gene. This alteration results from a G to A substitution at nucleotide position 122, causing the glycine (G) at amino acid position 41 to be replaced by a glutamic acid (E). 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
0.45
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
17
DANN
Benign
0.92
DEOGEN2
Benign
0.039
T;T;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.72
.;.;T
M_CAP
Benign
0.0011
T
MetaRNN
Pathogenic
0.79
D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.2
M;M;M
PrimateAI
Benign
0.28
T
PROVEAN
Pathogenic
-6.1
.;.;D
REVEL
Benign
0.092
Sift
Uncertain
0.0050
.;.;D
Sift4G
Uncertain
0.0070
.;.;D
Polyphen
0.67
P;P;P
Vest4
0.19
MutPred
0.81
Gain of catalytic residue at G41 (P = 0.1317);Gain of catalytic residue at G41 (P = 0.1317);Gain of catalytic residue at G41 (P = 0.1317);
MVP
0.53
MPC
0.094
ClinPred
0.88
D
GERP RS
1.7
Varity_R
0.76
gMVP
0.39

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: rs1248333088; hg19: chr19-14992046; API