11-55554719-C-A

Position:

• chr11-55554719-C-A

Variant summary

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

The NM_001001920.3(OR4C15):​c.251C>A​(p.Ser84Tyr) 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. 14/20 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)
• Consequence: OR4C15 NM_001001920.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.764

Genes affected

OR4C15 (HGNC:15171): (olfactory receptor family 4 subfamily C member 15) 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=0.17911196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4C15	NM_001001920.3	c.251C>A	p.Ser84Tyr	missense_variant	1/1	ENST00000642128.1	NP_001001920.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4C15	ENST00000642128.1	c.251C>A	p.Ser84Tyr	missense_variant	1/1		NM_001001920.3	ENSP00000493126.1
OR4C15	ENST00000314644.2	c.413C>A	p.Ser138Tyr	missense_variant	1/1	6		ENSP00000324958.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250918 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135612

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Jul 25, 2023

The c.413C>A (p.S138Y) alteration is located in exon 1 (coding exon 1) of the OR4C15 gene. This alteration results from a C to A substitution at nucleotide position 413, causing the serine (S) at amino acid position 138 to be replaced by a tyrosine (Y). 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	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.97
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.2	.;L
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.2	D;.
REVEL	Benign	0.10
Sift	Benign	0.050	D;.
Sift4G	Uncertain	0.042	D;.
Polyphen		0.84	.;P
Vest4		0.34
MutPred		0.43		.;Gain of methylation at K79 (P = 0.0637);
MVP		0.15
ClinPred		0.50	D
GERP RS		2.2
Varity_R		0.12
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs868758519; hg19: chr11-55322195;