9-104598758-G-A

Variant names:

• chr9-104598758-G-A
• rs111657456
• NM_001004482.1:c.656C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001004482.1(OR13C5):​c.656C>T​(p.Thr219Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,613,932 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (2 hom.)
• Consequence: OR13C5 NM_001004482.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.308
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.020704329).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.656C>T	p.Thr219Met	missense	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.656C>T	p.Thr219Met	missense	Exon 1 of 1	ENSP00000363911.2	Q8NGS8
	ENSG00000297079	ENST00000745188.1		n.370+23272C>T		intron	N/A
	ENSG00000297079	ENST00000745189.1		n.326+23272C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152058 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

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: 0.0000882

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.0000957 AC: 24 AN: 250786 AF XY: 0.0000591

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000140 AC: 205 AN: 1461756 Hom.: 2 Cov.: 54 AF XY: 0.000125 AC XY: 91 AN XY: 727178

African (AFR) AF: 0.00185 AC: 62 AN: 33466

American (AMR) AF: 0.000224 AC: 10 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000890 AC: 99 AN: 1111938

Other (OTH) AF: 0.000547 AC: 33 AN: 60380

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152176 Hom.: 1 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74382

African (AFR) AF: 0.000554 AC: 23 AN: 41534

American (AMR) AF: 0.000393 AC: 6 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 67994

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.0000745 Hom.: 0

Bravo AF: 0.000261

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.1
DANN	Benign	0.74
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.27	N
PhyloP100		-0.31
PrimateAI	Benign	0.17	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.027
Sift	Benign	0.33	T
Sift4G	Benign	0.28	T
Polyphen		0.0030	B
Vest4		0.080
MVP		0.12
MPC		0.25
ClinPred		0.0074	T
GERP RS		-0.54
Varity_R		0.021
gMVP		0.18
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs111657456; hg19: chr9-107361039; COSMIC: COSV66164556;