rs1360450855

Variant names:

• chrX-131544078-C-T
• rs1360450855
• NM_001004486.1:c.5C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-131544078-C-T
• chrX-131544078-C-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001004486.1(OR13H1):​c.5C>T​(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,172,005 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.000010 (0 hom. 3 hem.)
• Consequence: OR13H1 NM_001004486.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26
• Publications: 1 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.061943293).
• BS2: High Hemizygotes in GnomAd4 at 2 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.5C>T	p.Ala2Val	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.5C>T	p.Ala2Val	missense	Exon 1 of 1	ENSP00000340748.3	Q8NG92
	IGSF1	ENST00000370904.6	TSL:2	c.-913+34590G>A		intron	N/A	ENSP00000359941.1	Q8N6C5-2

Frequencies

GnomAD3 genomes AF: 0.0000357 AC: 4 AN: 112077 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000325

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000564

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000104 AC: 11 AN: 1059928 Hom.: 0 Cov.: 27 AF XY: 0.00000888 AC XY: 3 AN XY: 337966

African (AFR) AF: 0.00 AC: 0 AN: 25606

American (AMR) AF: 0.00 AC: 0 AN: 33151

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17301

East Asian (EAS) AF: 0.00 AC: 0 AN: 29833

South Asian (SAS) AF: 0.00 AC: 0 AN: 48708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39389

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3956

European-Non Finnish (NFE) AF: 0.0000122 AC: 10 AN: 817469

Other (OTH) AF: 0.0000225 AC: 1 AN: 44515

GnomAD4 genome AF: 0.0000357 AC: 4 AN: 112077 Hom.: 0 Cov.: 23 AF XY: 0.0000584 AC XY: 2 AN XY: 34257

African (AFR) AF: 0.0000325 AC: 1 AN: 30811

American (AMR) AF: 0.00 AC: 0 AN: 10586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3554

South Asian (SAS) AF: 0.00 AC: 0 AN: 2682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.0000564 AC: 3 AN: 53229

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.34
DANN	Benign	0.73
DEOGEN2	Benign	0.0066	T
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.78	N
PhyloP100		-1.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.012
Sift	Benign	0.22	T
Sift4G	Benign	0.29	T
Polyphen		0.031	B
Vest4		0.060
MutPred		0.18		Loss of disorder (P = 0.0889)
MVP		0.46
MPC		0.021
ClinPred		0.026	T
GERP RS		1.7
PromoterAI		-0.049	Neutral
Varity_R		0.045
gMVP		0.12
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1360450855; hg19: chrX-130678052; COSMIC: COSV100088251;