chrX-131544264-G-A

Position:

chrX-131544264-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001004486.1(OR13H1):c.191G>A(p.Ser64Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,208,201 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 50 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 0.000054 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.00012 ( 0 hom. 50 hem. )

Consequence

OR13H1
NM_001004486.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:2

Conservation

PhyloP100: 0.170

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15934756).

BS2

High Hemizygotes in GnomAdExome4 at 50 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR13H1	NM_001004486.1 linkuse as main transcript	c.191G>A	p.Ser64Asn	missense_variant	1/1	ENST00000338616.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR13H1	ENST00000338616.6 linkuse as main transcript	c.191G>A	p.Ser64Asn	missense_variant	1/1		NM_001004486.1	P1
IGSF1	ENST00000370904.6 linkuse as main transcript	c.-913+34404C>T		intron_variant		2			Q8N6C5-2

Frequencies

GnomAD3 genomes

AF:

0.0000536

AC:

AN:

111856

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34020

show subpopulations

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:

0.000165

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000941

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000546

AC:

AN:

183314

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

67802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.0000856

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000125

AC:

137

AN:

1096345

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

AN XY:

361721

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000173

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000536

AC:

AN:

111856

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34020

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000165

Gnomad4 NFE

AF:

0.0000941

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000162

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.191G>A (p.S64N) alteration is located in exon 1 (coding exon 1) of the OR13H1 gene. This alteration results from a G to A substitution at nucleotide position 191, causing the serine (S) at amino acid position 64 to be replaced by an asparagine (N). 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

0.22

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.86

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.013

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.32

M_CAP

Benign

0.0026

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.5

REVEL

Benign

0.035

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.030

Polyphen

0.92

Vest4

0.25

MVP

0.37

MPC

0.067

ClinPred

0.10

GERP RS

2.1

Varity_R

0.60

gMVP

0.33

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