19-14881295-G-A

Variant summary

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

The NM_030901.2(OR7A17):​c.61C>T​(p.Pro21Ser) 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 152,082 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

OR7A17
NM_030901.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.86
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0873754).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR7A17NM_030901.2 linkuse as main transcriptc.61C>T p.Pro21Ser missense_variant 3/3 ENST00000641113.1 NP_112163.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR7A17ENST00000641113.1 linkuse as main transcriptc.61C>T p.Pro21Ser missense_variant 3/3 NM_030901.2 ENSP00000493283 P1
OR7A17ENST00000642123.1 linkuse as main transcriptc.61C>T p.Pro21Ser missense_variant 3/3 ENSP00000493071 P1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152082
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.00
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248696
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134478
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:
0.00000889
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.87e-7
AC:
1
AN:
1455678
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
724010
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:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152082
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.00
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 GeneticsMar 28, 2024The c.61C>T (p.P21S) alteration is located in exon 1 (coding exon 1) of the OR7A17 gene. This alteration results from a C to T substitution at nucleotide position 61, causing the proline (P) at amino acid position 21 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
0.11
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
3.7
DANN
Benign
0.45
DEOGEN2
Benign
0.025
T;T;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.0087
N
LIST_S2
Benign
0.54
.;.;T
M_CAP
Benign
0.00057
T
MetaRNN
Benign
0.087
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.8
L;L;L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.18
T
PROVEAN
Uncertain
-4.0
.;.;D
REVEL
Benign
0.024
Sift
Benign
0.14
.;.;T
Sift4G
Benign
0.087
.;.;T
Polyphen
0.12
B;B;B
Vest4
0.16
MutPred
0.44
Loss of glycosylation at P21 (P = 0.033);Loss of glycosylation at P21 (P = 0.033);Loss of glycosylation at P21 (P = 0.033);
MVP
0.15
MPC
0.067
ClinPred
0.13
T
GERP RS
-5.5
Varity_R
0.035
gMVP
0.094

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: rs759505037; hg19: chr19-14992107; API