chr6-29355381-C-A

Variant names:

• chr6-29355381-C-A
• NM_030876.6:c.815G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030876.6(OR5V1):​c.815G>T​(p.Arg272Met) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R272G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR5V1 NM_030876.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.346
• Publications: 0 publications found

Genes affected

OR5V1 (HGNC:13972): (olfactory receptor family 5 subfamily V 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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22599623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5V1	NM_030876.6	c.815G>T	p.Arg272Met	missense_variant	Exon 2 of 2	ENST00000641768.1	NP_110503.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5V1	ENST00000641768.1	c.815G>T	p.Arg272Met	missense_variant	Exon 2 of 2		NM_030876.6	ENSP00000493269.1
OR5V1	ENST00000377154.1	c.815G>T	p.Arg272Met	missense_variant	Exon 4 of 4	6		ENSP00000366359.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.815G>T (p.R272M) alteration is located in exon 1 (coding exon 1) of the OR5V1 gene. This alteration results from a G to T substitution at nucleotide position 815, causing the arginine (R) at amino acid position 272 to be replaced by a methionine (M). 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	0.24
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.0061	T;T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.022	N
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;L
PhyloP100		-0.35
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-2.6	.;D;D
REVEL	Benign	0.093
Sift	Uncertain	0.0060	.;D;D
Sift4G	Uncertain	0.012	.;D;D
Polyphen		0.99	D;D;D
Vest4		0.32
MutPred		0.54		Gain of ubiquitination at K269 (P = 0.0388);Gain of ubiquitination at K269 (P = 0.0388);Gain of ubiquitination at K269 (P = 0.0388);
MVP		0.49
MPC		0.41
ClinPred		0.95	D
GERP RS		2.7
Varity_R		0.18
gMVP		0.34
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

hg19: chr6-29323158;