chrX-131544150-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

X-linked central congenital hypothyroidism with late-onset testicular enlargement
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

IGSF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 722682.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 53 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004486.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR13H1	NM_001004486.1	MANE Select	c.77C>T	p.Thr26Met	missense	Exon 1 of 1	NP_001004486.1	Q8NG92

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR13H1	ENST00000338616.6	TSL:6 MANE Select	c.77C>T	p.Thr26Met	missense	Exon 1 of 1	ENSP00000340748.3	Q8NG92
	IGSF1	ENST00000370904.6	TSL:2	c.-913+34518G>A		intron	N/A	ENSP00000359941.1	Q8N6C5-2

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

147

AN:

112029

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000379

AC:

AN:

182054

AF XY:

0.000360

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 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

African (AFR)

AF:

0.00397

AC:

104

AN:

26201

American (AMR)

AF:

0.000825

AC:

AN:

35144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19286

East Asian (EAS)

AF:

0.0000664

AC:

AN:

30120

South Asian (SAS)

AF:

0.000130

AC:

AN:

53703

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40511

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4106

European-Non Finnish (NFE)

AF:

0.0000264

AC:

AN:

832323

Other (OTH)

AF:

0.000569

AC:

AN:

45717

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00131

AC:

147

AN:

112085

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

AN XY:

34269

show subpopulations

African (AFR)

AF:

0.00318

AC:

AN:

30866

American (AMR)

AF:

0.00387

AC:

AN:

10583

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2655

East Asian (EAS)

AF:

0.000281

AC:

AN:

3554

South Asian (SAS)

AF:

0.00

AC:

AN:

2674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6135

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000564

AC:

AN:

53171

Other (OTH)

AF:

0.00259

AC:

AN:

1544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000527

Hom.:

Bravo

AF:

0.00232

ESP6500AA

AF:

0.00391

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000428

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.12

(source)

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

PhyloP100

-1.5

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

PromoterAI

0.0032

Neutral

(source)

Varity_R

0.022

gMVP

0.20

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over