9-104599168-T-A

Variant names:

• chr9-104599168-T-A
• rs79797302
• NM_001004482.1:c.246A>T
• OR13C5 p.Leu82Leu

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001004482.1(OR13C5):​c.246A>T​(p.Leu82Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L82L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000035 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR13C5 NM_001004482.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.725
• Publications: 3 publications found

Genes affected

OR13C5 (HGNC:15100): (olfactory receptor family 13 subfamily C 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]

ENSG00000297079 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-104599168-T-A is Benign according to our data. Variant chr9-104599168-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3388711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.725 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004482.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR13C5	NM_001004482.1	MANE Select	c.246A>T	p.Leu82Leu	synonymous	Exon 1 of 1	NP_001004482.1	Q8NGS8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR13C5	ENST00000374779.3	TSL:6 MANE Select	c.246A>T	p.Leu82Leu	synonymous	Exon 1 of 1	ENSP00000363911.2	Q8NGS8
	ENSG00000297079	ENST00000745188.1		n.370+22862A>T		intron	N/A
	ENSG00000297079	ENST00000745189.1		n.326+22862A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 142262 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000101 AC: 21 AN: 208496 AF XY: 0.0000890

Gnomad AFR exome AF: 0.0000861

Gnomad AMR exome AF: 0.000136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000106

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000349 AC: 5 AN: 1432018 Hom.: 0 Cov.: 41 AF XY: 0.00000140 AC XY: 1 AN XY: 713302

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31354

American (AMR) AF: 0.0000688 AC: 3 AN: 43618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.00 AC: 0 AN: 37696

South Asian (SAS) AF: 0.00 AC: 0 AN: 84706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1090746

Other (OTH) AF: 0.00 AC: 0 AN: 59180

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00594190), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 142262 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 69476

African (AFR) AF: 0.00 AC: 0 AN: 36328

American (AMR) AF: 0.00 AC: 0 AN: 14480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3426

East Asian (EAS) AF: 0.00 AC: 0 AN: 4284

South Asian (SAS) AF: 0.00 AC: 0 AN: 4504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65922

Other (OTH) AF: 0.00 AC: 0 AN: 2008

Alfa AF: 0.000316 Hom.: 2896

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.66
PhyloP100		-0.72
PromoterAI		0.0012	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs79797302;

hg19: chr9-107361449;