19-110890-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001005240.3(OR4F17):​c.212C>A​(p.Ala71Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. A71V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 25)
Exomes 𝑓: 0.0000060 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

OR4F17
NM_001005240.3 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0500
Variant links:
Genes affected
OR4F17 (HGNC:15381): (olfactory receptor family 4 subfamily F 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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34613514).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR4F17NM_001005240.3 linkc.212C>A p.Ala71Asp missense_variant Exon 3 of 3 ENST00000585993.3 NP_001005240.1 Q8NGA8A0A126GWN0
OR4F17NM_001429985.1 linkc.275C>A p.Ala92Asp missense_variant Exon 2 of 2 NP_001416914.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR4F17ENST00000585993.3 linkc.212C>A p.Ala71Asp missense_variant Exon 3 of 3 6 NM_001005240.3 ENSP00000467301.1 Q8NGA8
OR4F17ENST00000618231.3 linkc.275C>A p.Ala92Asp missense_variant Exon 2 of 2 6 ENSP00000493422.2 A0A2U3U062
OR4F17ENST00000318050.4 linkc.212C>A p.Ala71Asp missense_variant Exon 1 of 1 6 ENSP00000315047.3 Q8NGA8
OR4F17ENST00000641591.1 linkn.194+209C>A intron_variant Intron 3 of 3

Frequencies

GnomAD3 genomes
Cov.:
25
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000598
AC:
8
AN:
1337558
Hom.:
0
Cov.:
25
AF XY:
0.00000447
AC XY:
3
AN XY:
670808
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:
0.00000798
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
25

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.212C>A (p.A71D) alteration is located in exon 1 (coding exon 1) of the OR4F17 gene. This alteration results from a C to A substitution at nucleotide position 212, causing the alanine (A) at amino acid position 71 to be replaced by an aspartic acid (D). 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
Pathogenic
0.80
BayesDel_addAF
Benign
0.0011
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.016
T;.;T
Eigen
Benign
-0.0091
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.096
N
LIST_S2
Benign
0.57
.;T;T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.35
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M;.;M
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-2.6
.;.;D
REVEL
Benign
0.20
Sift
Uncertain
0.0010
.;.;D
Sift4G
Pathogenic
0.0010
D;.;D
Polyphen
1.0
D;.;D
Vest4
0.60
MutPred
0.75
Gain of disorder (P = 0.0324);.;Gain of disorder (P = 0.0324);
MVP
0.72
MPC
4.6
ClinPred
0.96
D
GERP RS
1.2
Varity_R
0.65
gMVP
0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-110890; API