1-159440372-A-G

Position:

• chr1-159440372-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_012351.3(OR10J1):​c.581A>G​(p.Asn194Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000341 in 1,614,162 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (2 hom.)
• Consequence: OR10J1 NM_012351.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0240

Genes affected

OR10J1 (HGNC:8175): (olfactory receptor family 10 subfamily J 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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022284746).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10J1	NM_012351.3	c.581A>G	p.Asn194Ser	missense_variant	1/1	ENST00000423932.6
OR10J1	NM_001363557.2	c.581A>G	p.Asn194Ser	missense_variant	5/5
OR10J1	NM_001363558.2	c.581A>G	p.Asn194Ser	missense_variant	4/4
OR10J1	XM_047417793.1	c.581A>G	p.Asn194Ser	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10J1	ENST00000423932.6	c.581A>G	p.Asn194Ser	missense_variant	1/1		NM_012351.3	P1
	ENST00000431862.1	n.227+28470T>C		intron_variant, non_coding_transcript_variant		1
OR10J1	ENST00000641630.1	c.614A>G	p.Asn205Ser	missense_variant	1/1
OR10J1	ENST00000642080.1	c.581A>G	p.Asn194Ser	missense_variant	2/2			P1

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000286 AC: 72 AN: 251410 Hom.: 0 AF XY: 0.000287 AC XY: 39 AN XY: 135880

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000440

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000356 AC: 520 AN: 1461880 Hom.: 2 Cov.: 36 AF XY: 0.000342 AC XY: 249 AN XY: 727242

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00134

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.000391

Gnomad4 OTH exome AF: 0.000381

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74458

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000385 Hom.: 0

Bravo AF: 0.000204

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000296 AC: 36

EpiCase AF: 0.000382

EpiControl AF: 0.000356

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

Dec 21, 2022

The c.614A>G (p.N205S) alteration is located in exon 1 (coding exon 1) of the OR10J1 gene. This alteration results from a A to G substitution at nucleotide position 614, causing the asparagine (N) at amino acid position 205 to be replaced by a serine (S). 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	0.099
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.013	.;T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.17	.;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.022	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.66	.;N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.20	T
REVEL	Benign	0.031
Polyphen		0.43	.;B;.
MVP		0.20
MPC		0.0096
ClinPred		0.039	T
GERP RS		2.0
Varity_R		0.068
gMVP		0.047

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs140818033; hg19: chr1-159410162;