Genetic Variant OR13C5:p.Thr219Met (chr9-104598758-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

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. 15/21 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.308

Variant links:

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]

OR13C5 links:

LOC107987105 (HGNC:):

LOC107987105 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020704329).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR13C5	NM_001004482.1 link	c.656C>T	p.Thr219Met	missense_variant	Exon 1 of 1	ENST00000374779.3	NP_001004482.1	Q8NGS8
LOC107987105	XR_007061705.1 link	n.427+23272C>T		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR13C5	ENST00000374779.3 link	c.656C>T	p.Thr219Met	missense_variant	Exon 1 of 1	6	NM_001004482.1	ENSP00000363911.2		Q8NGS8

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0000957

AC:

AN:

250786

Hom.:

AF XY:

0.0000591

AC XY:

AN XY:

135476

show subpopulations

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 SAS exome

AF:

0.0000327

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.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00185

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000890

Gnomad4 OTH exome

AF:

0.000547

GnomAD4 genome

AF:

0.000243

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.0000745

Hom.:

Bravo

AF:

0.000261

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 11, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.656C>T (p.T219M) alteration is located in exon 1 (coding exon 1) of the OR13C5 gene. This alteration results from a C to T substitution at nucleotide position 656, causing the threonine (T) at amino acid position 219 to be replaced by a methionine (M). 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

0.076

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.1

DANN

Benign

0.74

DEOGEN2

Benign

0.0046

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.33

M_CAP

Benign

0.0011

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.27

PrimateAI

Benign

0.17

PROVEAN

Benign

1.1

REVEL

Benign

0.027

Sift

Benign

0.33

Sift4G

Benign

0.28

Polyphen

0.0030

Vest4

0.080

MVP

0.12

MPC

0.25

ClinPred

0.0074

GERP RS

-0.54

Varity_R

0.021

gMVP

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over