chr15-22095104-G-A

Position:

• chr15-22095104-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005241.4(OR4N4):​c.583G>A​(p.Val195Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 10)
  • Exomes 𝑓: 0.0000024 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4N4 NM_001005241.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.557

Genes affected

OR4N4 (HGNC:15375): (olfactory receptor family 4 subfamily N member 4) 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]

OR4M2-OT1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2004419).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR4N4	NM_001005241.4	c.583G>A	p.Val195Met	missense_variant	1/1	ENST00000328795.6
OR4M2-OT1	NR_110480.1	n.1103-247G>A		intron_variant, non_coding_transcript_variant
OR4M2-OT1	NR_110481.1	n.835-247G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4N4	ENST00000328795.6	c.583G>A	p.Val195Met	missense_variant	1/1		NM_001005241.4	P1

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000236 AC: 2 AN: 846102 Hom.: 1 Cov.: 24 AF XY: 0.00000473 AC XY: 2 AN XY: 422644

Gnomad4 AFR exome AF: 0.0000887

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 10

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

Jun 10, 2024

The c.583G>A (p.V195M) alteration is located in exon 1 (coding exon 1) of the OR4N4 gene. This alteration results from a G to A substitution at nucleotide position 583, causing the valine (V) at amino acid position 195 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	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.58
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0040	.;T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.81	T;.
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.2	.;L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.88	.;N
REVEL	Benign	0.061
Sift	Uncertain	0.027	.;D
Sift4G	Uncertain	0.015	.;D
Polyphen		0.96	.;D
Vest4		0.22
MutPred		0.35		Loss of catalytic residue at V195 (P = 0.0013);Loss of catalytic residue at V195 (P = 0.0013);
MVP		0.30
MPC		0.41
ClinPred		0.71	D
GERP RS		3.4
Varity_R		0.11
gMVP		0.13

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: rs1202387541; hg19: chr15-22383055;