NM_001004482.1:c.766T>G

Variant names:

• chr9-104598648-A-C
• rs745320731
• NM_001004482.1:c.766T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004482.1(OR13C5):​c.766T>G​(p.Phe256Val) 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 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F256L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR13C5 NM_001004482.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 0 publications found

Genes affected

OR13C5 (HGNC:15100): (olfactory receptor family 13 subfamily C 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]

ENSG00000297079 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058529824).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004482.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR13C5	NM_001004482.1	MANE Select	c.766T>G	p.Phe256Val	missense	Exon 1 of 1	NP_001004482.1	Q8NGS8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR13C5	ENST00000374779.3	TSL:6 MANE Select	c.766T>G	p.Phe256Val	missense	Exon 1 of 1	ENSP00000363911.2	Q8NGS8
	ENSG00000297079	ENST00000745188.1		n.370+23382T>G		intron	N/A
	ENSG00000297079	ENST00000745189.1		n.326+23382T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461708 Hom.: 0 Cov.: 54 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111912

Other (OTH) AF: 0.0000166 AC: 1 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.75
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.94	L
PhyloP100		-1.1
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.014
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.060	T
Polyphen		0.0010	B
Vest4		0.061
MutPred		0.30		Gain of catalytic residue at M260 (P = 0.0337)
MVP		0.18
MPC		0.27
ClinPred		0.088	T
GERP RS		2.1
Varity_R		0.091
gMVP		0.10
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs745320731; hg19: chr9-107360929; COSMIC: COSV66164562;