17-3062892-G-C

Position:

• chr17-3062892-G-C

Variant summary

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

The NM_014566.1(OR1D5):​c.716C>G​(p.Ser239Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 42)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR1D5 NM_014566.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70

Genes affected

OR1D5 (HGNC:8186): (olfactory receptor family 1 subfamily D member 5) 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]

ACMG classification

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
OR1D5	NM_014566.1	c.716C>G	p.Ser239Cys	missense_variant	1/1	ENST00000575751.1	NP_055381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR1D5	ENST00000575751.1	c.716C>G	p.Ser239Cys	missense_variant	1/1		NM_014566.1	ENSP00000459028	P1

Frequencies

GnomAD3 genomes Cov.: 42

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000205 AC: 3 AN: 1461782 Hom.: 0 Cov.: 83 AF XY: 0.00000275 AC XY: 2 AN XY: 727176

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 42

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.716C>G (p.S239C) alteration is located in exon 1 (coding exon 1) of the OR1D5 gene. This alteration results from a C to G substitution at nucleotide position 716, causing the serine (S) at amino acid position 239 to be replaced by a cysteine (C). 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	0.13
BayesDel_addAF	Benign	0.0073	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	T
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0086	T
MetaRNN	Uncertain	0.65	D
MutationAssessor	Pathogenic	4.0	H
MutationTaster	Benign	0.98	N
PrimateAI	Benign	0.25	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.56
MVP		0.86
MPC		2.6
GERP RS		3.5
Varity_R		0.14
gMVP		0.040

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

LitVar

Other links and lift over

dbSNP: rs780977611; hg19: chr17-2966186;