1-247815209-T-C

Variant summary

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

The NM_001001966.2(OR14A16):​c.521A>G​(p.Gln174Arg) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

OR14A16
NM_001001966.2 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24
Variant links:
Genes affected
OR14A16 (HGNC:15022): (olfactory receptor family 14 subfamily A member 16) 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]

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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, 0.764

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR14A16NM_001001966.2 linkuse as main transcriptc.521A>G p.Gln174Arg missense_variant 3/3 ENST00000641093.1 NP_001001966.1 Q8NHC5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR14A16ENST00000641093.1 linkuse as main transcriptc.521A>G p.Gln174Arg missense_variant 3/3 NM_001001966.2 ENSP00000493024.1 Q8NHC5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
33

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 03, 2024The c.521A>G (p.Q174R) alteration is located in exon 1 (coding exon 1) of the OR14A16 gene. This alteration results from a A to G substitution at nucleotide position 521, causing the glutamine (Q) at amino acid position 174 to be replaced by an arginine (R). 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
0.12
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.015
T;T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.79
.;T
M_CAP
Benign
0.00038
T
MetaRNN
Pathogenic
0.76
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
M;M
PrimateAI
Benign
0.24
T
PROVEAN
Uncertain
-3.8
.;D
REVEL
Benign
0.12
Sift
Uncertain
0.023
.;D
Sift4G
Uncertain
0.0060
.;D
Polyphen
0.93
P;P
Vest4
0.22
MutPred
0.78
Loss of glycosylation at S169 (P = 0.299);Loss of glycosylation at S169 (P = 0.299);
MVP
0.055
MPC
0.34
ClinPred
0.98
D
GERP RS
3.5
Varity_R
0.76
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: chr1-247978511; API