12-48525690-A-T

Position:

• chr12-48525690-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001390849.1(OR8S1):​c.59A>T​(p.Asp20Val) 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. 14/20 in silico tools predict a benign outcome for this variant. 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: -2.02

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16533452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR8S1	NM_001390849.1	c.59A>T	p.Asp20Val	missense_variant	1/1	ENST00000641651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR8S1	ENST00000641651.1	c.59A>T	p.Asp20Val	missense_variant	1/1		NM_001390849.1	P1
	ENST00000551654.1	n.184-2182A>T		intron_variant, non_coding_transcript_variant

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2022

The c.59A>T (p.D20V) alteration is located in exon 1 (coding exon 1) of the OR8S1 gene. This alteration results from a A to T substitution at nucleotide position 59, causing the aspartic acid (D) at amino acid position 20 to be replaced by a valine (V). 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	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.89
DEOGEN2	Benign	0.023	.;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.0091	T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	.;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.19	T
PROVEAN	Pathogenic	-5.8	.;D
REVEL	Benign	0.058
Sift	Benign	0.21	.;T
Sift4G	Benign	0.20	.;T
Polyphen		0.39	.;B
Vest4		0.17
MutPred		0.56		Gain of catalytic residue at A19 (P = 0.0097);Gain of catalytic residue at A19 (P = 0.0097);
MVP		0.32
MPC		0.061
ClinPred		0.30	T
GERP RS		1.3
Varity_R		0.055

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-48919473;