rs1565070119

Variant names:

• chr11-59422092-G-A
• NM_001001954.2:c.862C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-59422092-G-A
• chr11-59422092-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001001954.2(OR5A2):​c.862C>T​(p.Pro288Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OR5A2 NM_001001954.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.92

Genes affected

OR5A2 (HGNC:15249): (olfactory receptor family 5 subfamily A member 2) 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.864

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5A2	NM_001001954.2	c.862C>T	p.Pro288Ser	missense_variant	Exon 2 of 2	ENST00000302040.6	NP_001001954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5A2	ENST00000302040.6	c.862C>T	p.Pro288Ser	missense_variant	Exon 2 of 2	6	NM_001001954.2	ENSP00000303834.4
OR5A2	ENST00000641361.1	c.862C>T	p.Pro288Ser	missense_variant	Exon 2 of 2			ENSP00000493065.1
OR5A2	ENST00000641673.1	c.862C>T	p.Pro288Ser	missense_variant	Exon 1 of 1			ENSP00000492975.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461830 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	.;.;D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.6	L;L;L
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-7.2	D;.;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.011	D;.;.
Sift4G	Uncertain	0.0080	D;.;.
Polyphen		0.98	D;D;D
Vest4		0.51
MutPred		0.65		Gain of MoRF binding (P = 0.0537);Gain of MoRF binding (P = 0.0537);Gain of MoRF binding (P = 0.0537);
MVP		0.84
MPC		0.10
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.69
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-59189565;