12-48526356-C-A

Position:

• chr12-48526356-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001390849.1(OR8S1):​c.725C>A​(p.Ser242Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR8S1 NM_001390849.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.129

Genes affected

OR8S1 (HGNC:19628): (olfactory receptor family 8 subfamily S 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]

ENSG00000197376 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR8S1	NM_001390849.1	c.725C>A	p.Ser242Tyr	missense_variant	1/1	ENST00000641651.1	NP_001377778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR8S1	ENST00000641651.1	c.725C>A	p.Ser242Tyr	missense_variant	1/1		NM_001390849.1	ENSP00000493379.1
ENSG00000197376	ENST00000551654.1	n.184-1516C>A		intron_variant		6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

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

Aug 02, 2022

The c.725C>A (p.S242Y) alteration is located in exon 1 (coding exon 1) of the OR8S1 gene. This alteration results from a C to A substitution at nucleotide position 725, causing the serine (S) at amino acid position 242 to be replaced by a tyrosine (Y). 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	0.14
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0070	.;T
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Pathogenic	3.8	.;H
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-5.1	.;D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0010	.;D
Polyphen		0.79	.;P
Vest4		0.37
MutPred		0.56		Gain of catalytic residue at H244 (P = 5e-04);Gain of catalytic residue at H244 (P = 5e-04);
MVP		0.50
MPC		0.26
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs1198090426; hg19: chr12-48920139;