X-131544889-T-A

Position:

chrX-131544889-T-A

Variant summary

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

The NM_001004486.1(OR13H1):c.816T>A(p.Phe272Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,207,241 control chromosomes in the GnomAD database, including 3 homozygotes. There are 539 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., 24 hem., cov: 23)

Exomes 𝑓: 0.0014 ( 2 hom. 515 hem. )

Consequence

OR13H1
NM_001004486.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.220

Variant links:

Genes affected

OR13H1 (HGNC:14755): (olfactory receptor family 13 subfamily H 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]

OR13H1 links:

IGSF1 (HGNC:5948): (immunoglobulin superfamily member 1) This gene encodes a member of the immunoglobulin-like domain-containing superfamily. Proteins in this superfamily contain varying numbers of immunoglobulin-like domains and are thought to participate in the regulation of interactions between cells. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

IGSF1 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=0.007773459).

BS2

High Hemizygotes in GnomAd4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR13H1	NM_001004486.1 link	c.816T>A	p.Phe272Leu	missense_variant	1/1	ENST00000338616.6	NP_001004486.1	Q8NG92A0A126GW70

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR13H1	ENST00000338616.6 link	c.816T>A	p.Phe272Leu	missense_variant	1/1	6	NM_001004486.1	ENSP00000340748.3		Q8NG92
IGSF1	ENST00000370904.6 link	c.-913+33779A>T		intron_variant		2		ENSP00000359941.1		Q8N6C5-2

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

128

AN:

111916

Hom.:

Cov.:

AF XY:

0.000704

AC XY:

AN XY:

34072

show subpopulations

Gnomad AFR

AF:

0.000195

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000570

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000752

Gnomad FIN

AF:

0.00131

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.000394

AC:

AN:

182920

Hom.:

AF XY:

0.000281

AC XY:

AN XY:

67536

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000210

Gnomad FIN exome

AF:

0.000375

Gnomad NFE exome

AF:

0.000663

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00144

AC:

1578

AN:

1095273

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

515

AN XY:

360697

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.000284

Gnomad4 ASJ exome

AF:

0.000361

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000555

Gnomad4 FIN exome

AF:

0.00131

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00114

AC:

128

AN:

111968

Hom.:

Cov.:

AF XY:

0.000703

AC XY:

AN XY:

34134

show subpopulations

Gnomad4 AFR

AF:

0.000195

Gnomad4 AMR

AF:

0.000569

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000754

Gnomad4 FIN

AF:

0.00131

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.000735

Hom.:

ExAC

AF:

0.000997

AC:

121

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

Dec 19, 2023

The c.816T>A (p.F272L) alteration is located in exon 1 (coding exon 1) of the OR13H1 gene. This alteration results from a T to A substitution at nucleotide position 816, causing the phenylalanine (F) at amino acid position 272 to be replaced by a leucine (L). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.49

DEOGEN2

Benign

0.0017

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.46

M_CAP

Benign

0.0016

MetaRNN

Benign

0.0078

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.72

PrimateAI

Benign

0.35

PROVEAN

Benign

1.4

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

0.80

Polyphen

0.0070

Vest4

0.012

MutPred

0.32

Gain of catalytic residue at F272 (P = 0.0852);

MVP

0.67

MPC

0.023

ClinPred

0.024

GERP RS

1.1

Varity_R

0.11

gMVP

0.062

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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