19-9214053-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001005191.3(OR7D4):​c.785C>T​(p.Ser262Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR7D4
NM_001005191.3 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38
Variant links:
Genes affected
OR7D4 (HGNC:8380): (olfactory receptor family 7 subfamily D member 4) 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]
OR7E24 (HGNC:8396): (olfactory receptor family 7 subfamily E member 24) 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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR7D4NM_001005191.3 linkuse as main transcriptc.785C>T p.Ser262Phe missense_variant 2/2 ENST00000641669.1 NP_001005191.1 Q8NG98A0A126GVR1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR7D4ENST00000641669.1 linkuse as main transcriptc.785C>T p.Ser262Phe missense_variant 2/2 NM_001005191.3 ENSP00000493383.1 Q8NG98
OR7D4ENST00000308682.3 linkuse as main transcriptc.785C>T p.Ser262Phe missense_variant 1/16 ENSP00000310488.2 Q8NG98
OR7D4ENST00000641244.1 linkuse as main transcriptc.785C>T p.Ser262Phe missense_variant 2/2 ENSP00000493404.1 Q8NG98

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461892
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
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:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsMay 28, 2024The c.785C>T (p.S262F) alteration is located in exon 1 (coding exon 1) of the OR7D4 gene. This alteration results from a C to T substitution at nucleotide position 785, causing the serine (S) at amino acid position 262 to be replaced by a phenylalanine (F). 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
0.17
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0094
T;T;T
Eigen
Benign
-0.0034
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.076
N
LIST_S2
Benign
0.78
.;.;T
M_CAP
Benign
0.0019
T
MetaRNN
Uncertain
0.46
T;T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Uncertain
2.6
M;M;M
PrimateAI
Benign
0.21
T
PROVEAN
Pathogenic
-5.6
.;.;D
REVEL
Benign
0.064
Sift
Uncertain
0.010
.;.;D
Sift4G
Uncertain
0.028
.;.;D
Polyphen
0.99
D;D;D
Vest4
0.10
MutPred
0.67
Loss of disorder (P = 0.0022);Loss of disorder (P = 0.0022);Loss of disorder (P = 0.0022);
MVP
0.60
MPC
0.13
ClinPred
0.87
D
GERP RS
3.7
Varity_R
0.42
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr19-9324729; API