1-159535412-T-A

Position:

• chr1-159535412-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001004469.1(OR10J5):​c.596A>T​(p.Tyr199Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 1,613,954 control chromosomes in the GnomAD database, including 434 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (226 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (208 hom.)
• Consequence: OR10J5 NM_001004469.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.05

Genes affected

OR10J5 (HGNC:14993): (olfactory receptor family 10 subfamily J member 5) 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]

ENSG00000289484 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015038848).
• BP6: Variant 1-159535412-T-A is Benign according to our data. Variant chr1-159535412-T-A is described in ClinVar as [Benign]. Clinvar id is 780786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10J5	NM_001004469.1	c.596A>T	p.Tyr199Phe	missense_variant	1/1	ENST00000334857.3	NP_001004469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10J5	ENST00000334857.3	c.596A>T	p.Tyr199Phe	missense_variant	1/1	6	NM_001004469.1	ENSP00000334441.2
ENSG00000289484	ENST00000693113.1	n.755-32137A>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 4292 AN: 152110 Hom.: 225 Cov.: 32

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00773 AC: 1939 AN: 250770 Hom.: 91 AF XY: 0.00575 AC XY: 779 AN XY: 135534

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.00483

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00507

GnomAD4 exome AF: 0.00301 AC: 4403 AN: 1461724 Hom.: 208 Cov.: 33 AF XY: 0.00263 AC XY: 1913 AN XY: 727206

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.00503

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000121

Gnomad4 OTH exome AF: 0.00594

GnomAD4 genome AF: 0.0283 AC: 4302 AN: 152230 Hom.: 226 Cov.: 32 AF XY: 0.0266 AC XY: 1980 AN XY: 74438

Gnomad4 AFR AF: 0.0987

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.00446 Hom.: 27

Bravo AF: 0.0327

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0987 AC: 435

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00943 AC: 1145

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.2
DANN	Benign	0.095
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.51	N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	2.1	N
REVEL	Benign	0.096
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.14
MVP		0.20
MPC		0.037
ClinPred		0.0046	T
GERP RS		1.4
Varity_R		0.16
gMVP		0.062

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

LitVar

Other links and lift over

dbSNP: rs56786307; hg19: chr1-159505202;