11-56319012-G-T

Variant names:

• chr11-56319012-G-T
• rs372838650
• NM_001005202.2:c.706G>T

Variant summary

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

The NM_001005202.2(OR8K3):​c.706G>T​(p.Ala236Ser) 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 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A236T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR8K3 NM_001005202.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49
• Publications: 0 publications found

Genes affected

OR8K3 (HGNC:15313): (olfactory receptor family 8 subfamily K member 3 (gene/pseudogene)) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005202.2. 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
	OR8K3	NM_001005202.2	MANE Select	c.706G>T	p.Ala236Ser	missense	Exon 3 of 3	NP_001005202.1	Q8NH51

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8K3	ENST00000641662.1	MANE Select	c.706G>T	p.Ala236Ser	missense	Exon 3 of 3	ENSP00000493271.1	Q8NH51
	OR8K3	ENST00000641689.1		c.706G>T	p.Ala236Ser	missense	Exon 2 of 2	ENSP00000493440.1	Q8NH51

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461826 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0014	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		3.5
PrimateAI	Benign	0.22	T
Polyphen		0.97	D
MutPred		0.58		Gain of disorder (P = 0.0211)
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.27
gMVP		0.053
Mutation Taster		=89/11	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

dbSNP: rs372838650; hg19: chr11-56086488;