Variant chrX-131544150-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001004486.1(OR13H1):c.77C>T(p.Thr26Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000281 in 1,199,196 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 100 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., 53 hem., cov: 23)

Exomes 𝑓: 0.00017 ( 0 hom. 47 hem. )

Consequence

OR13H1
NM_001004486.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.50

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008033007).

BP6

Variant X-131544150-C-T is Benign according to our data. Variant chrX-131544150-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 722682.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 53 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR13H1	NM_001004486.1 linkuse as main transcript	c.77C>T	p.Thr26Met	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.77C>T	p.Thr26Met	missense_variant	1/1		NM_001004486.1	P1
IGSF1	ENST00000370904.6 linkuse as main transcript	c.-913+34518G>A		intron_variant		2			Q8N6C5-2

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

147

AN:

112029

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

AN XY:

34203

show subpopulations

Gnomad AFR

AF:

0.00318

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00388

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000564

Gnomad OTH

AF:

0.00262

GnomAD3 exomes

AF:

0.000379

AC:

AN:

182054

Hom.:

AF XY:

0.000360

AC XY:

AN XY:

66634

show subpopulations

Gnomad AFR exome

AF:

0.00334

Gnomad AMR exome

AF:

0.000476

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.000215

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000492

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.000175

AC:

190

AN:

1087111

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

352997

show subpopulations

Gnomad4 AFR exome

AF:

0.00397

Gnomad4 AMR exome

AF:

0.000825

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000664

Gnomad4 SAS exome

AF:

0.000130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000264

Gnomad4 OTH exome

AF:

0.000569

GnomAD4 genome

AF:

0.00131

AC:

147

AN:

112085

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

AN XY:

34269

show subpopulations

Gnomad4 AFR

AF:

0.00318

Gnomad4 AMR

AF:

0.00387

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000564

Gnomad4 OTH

AF:

0.00259

Alfa

AF:

0.000153

Hom.:

Bravo

AF:

0.00232

ESP6500AA

AF:

0.00391

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000428

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.12

DANN

Benign

0.97

DEOGEN2

Benign

0.0061

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.36

M_CAP

Benign

0.0027

MetaRNN

Benign

0.0080

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.61

MutationTaster

Benign

1.0

PrimateAI

Benign

0.17

PROVEAN

Benign

0.36

REVEL

Benign

0.13

Sift

Benign

0.090

Sift4G

Benign

0.090

Polyphen

1.0

Vest4

0.018

MVP

0.44

MPC

0.021

ClinPred

0.0094

GERP RS

-1.5

Varity_R

0.022

gMVP

0.20

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