17-58155500-C-T

Variant names:

• chr17-58155500-C-T
• NM_001386095.1:c.347C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001386095.1(OR4D1):​c.347C>T​(p.Ser116Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OR4D1 NM_001386095.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35

Genes affected

OR4D1 (HGNC:8293): (olfactory receptor family 4 subfamily D member 1) 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23804635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4D1	NM_001386095.1	c.347C>T	p.Ser116Leu	missense_variant	Exon 4 of 4	ENST00000268912.6	NP_001373024.1
OR4D1	NM_012374.2	c.347C>T	p.Ser116Leu	missense_variant	Exon 3 of 3		NP_036506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4D1	ENST00000268912.6	c.347C>T	p.Ser116Leu	missense_variant	Exon 4 of 4	6	NM_001386095.1	ENSP00000365451.3
OR4D1	ENST00000641449.1	c.347C>T	p.Ser116Leu	missense_variant	Exon 3 of 3			ENSP00000493234.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461876 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.347C>T (p.S116L) alteration is located in exon 1 (coding exon 1) of the OR4D1 gene. This alteration results from a C to T substitution at nucleotide position 347, causing the serine (S) at amino acid position 116 to be replaced by a leucine (L). 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	0.18
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0046	T;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.057
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	0.12	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.0	.;D
REVEL	Benign	0.13
Sift	Benign	0.078	.;T
Sift4G	Benign	0.080	.;T
Polyphen		0.97	D;D
Vest4		0.20
MutPred		0.43		Loss of catalytic residue at S116 (P = 0.0018);Loss of catalytic residue at S116 (P = 0.0018);
MVP		0.63
MPC		0.082
ClinPred		0.94	D
GERP RS		4.7
Varity_R		0.37
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-56232861;