Variant 3-98149885-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005514.2(OR5H14):c.500C>T(p.Thr167Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

OR5H14
NM_001005514.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.545

Variant links:

Genes affected

OR5H14 (HGNC:31286): (olfactory receptor family 5 subfamily H member 14) 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]

OR5H14 links:

LOC105373996 (HGNC:):

LOC105373996 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14455041).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5H14	NM_001005514.2 linkuse as main transcript	c.500C>T	p.Thr167Ile	missense_variant	2/2	ENST00000641380.1	NP_001005514.1	A6NHG9
LOC105373996	XR_924253.2 linkuse as main transcript	n.238-1721G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5H14	ENST00000641380.1 linkuse as main transcript	c.500C>T	p.Thr167Ile	missense_variant	2/2		NM_001005514.2	ENSP00000493226.1		A6NHG9
OR5H14	ENST00000437310.1 linkuse as main transcript	c.500C>T	p.Thr167Ile	missense_variant	1/1	6		ENSP00000401706.1		A6NHG9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250832

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461222

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726934

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2024

The c.500C>T (p.T167I) alteration is located in exon 1 (coding exon 1) of the OR5H14 gene. This alteration results from a C to T substitution at nucleotide position 500, causing the threonine (T) at amino acid position 167 to be replaced by an isoleucine (I). 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

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.73

.;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-4.4

.;D

REVEL

Benign

0.033

Sift

Uncertain

0.028

.;D

Sift4G

Benign

0.076

.;T

Polyphen

0.53

P;P

Vest4

0.064

MutPred

0.36

Loss of glycosylation at S171 (P = 0.1391);Loss of glycosylation at S171 (P = 0.1391);

MVP

0.099

MPC

0.019

ClinPred

0.71

GERP RS

1.5

Varity_R

0.25

gMVP

0.11

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

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