1-159440105-T-C

Variant names:

• chr1-159440105-T-C
• rs138020603
• NM_012351.3:c.314T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012351.3(OR10J1):​c.314T>C​(p.Val105Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: OR10J1 NM_012351.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00900

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]

ENSG00000228560 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028546274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10J1	NM_012351.3	c.314T>C	p.Val105Ala	missense_variant	Exon 1 of 1	ENST00000423932.6	NP_036483.3
OR10J1	NM_001363557.2	c.314T>C	p.Val105Ala	missense_variant	Exon 5 of 5		NP_001350486.1
OR10J1	NM_001363558.2	c.314T>C	p.Val105Ala	missense_variant	Exon 4 of 4		NP_001350487.1
OR10J1	XM_047417793.1	c.314T>C	p.Val105Ala	missense_variant	Exon 2 of 2		XP_047273749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR10J1	ENST00000423932.6	c.314T>C	p.Val105Ala	missense_variant	Exon 1 of 1	6	NM_012351.3	ENSP00000399078.4
ENSG00000228560	ENST00000431862.1	n.227+28737A>G		intron_variant	Intron 1 of 3	1
OR10J1	ENST00000641630.1	c.347T>C	p.Val116Ala	missense_variant	Exon 1 of 1			ENSP00000492902.1
OR10J1	ENST00000642080.1	c.314T>C	p.Val105Ala	missense_variant	Exon 2 of 2			ENSP00000493228.1

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000263 AC: 66 AN: 251382 Hom.: 0 AF XY: 0.000287 AC XY: 39 AN XY: 135856

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000422

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000217 AC: 317 AN: 1461854 Hom.: 0 Cov.: 36 AF XY: 0.000246 AC XY: 179 AN XY: 727224

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000267

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74344

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.000955

Alfa AF: 0.000343 Hom.: 0

Bravo AF: 0.000261

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000288 AC: 35

EpiCase AF: 0.000327

EpiControl AF: 0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.347T>C (p.V116A) alteration is located in exon 1 (coding exon 1) of the OR10J1 gene. This alteration results from a T to C substitution at nucleotide position 347, causing the valine (V) at amino acid position 116 to be replaced by an alanine (A). 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	0.22
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0079	.;T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.28	.;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.029	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	-0.080	.;N;.
PrimateAI	Benign	0.21	T
REVEL	Benign	0.13
Polyphen		0.0	.;B;.
MVP		0.11
MPC		0.0060
ClinPred		0.0091	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.060

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: rs138020603; hg19: chr1-159409895;