X-131544134-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001004486.1(OR13H1):​c.61C>T​(p.Pro21Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000919 in 1,088,407 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P21L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

OR13H1
NM_001004486.1 missense

Scores

1
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0400
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40719864).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR13H1NM_001004486.1 linkc.61C>T p.Pro21Ser missense_variant Exon 1 of 1 ENST00000338616.6 NP_001004486.1 Q8NG92A0A126GW70

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR13H1ENST00000338616.6 linkc.61C>T p.Pro21Ser missense_variant Exon 1 of 1 6 NM_001004486.1 ENSP00000340748.3 Q8NG92
IGSF1ENST00000370904.6 linkc.-913+34534G>A intron_variant Intron 1 of 26 2 ENSP00000359941.1 Q8N6C5-2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
9.19e-7
AC:
1
AN:
1088407
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
354591
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000285
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.61C>T (p.P21S) alteration is located in exon 1 (coding exon 1) of the OR13H1 gene. This alteration results from a C to T substitution at nucleotide position 61, causing the proline (P) at amino acid position 21 to be replaced by a serine (S). 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
0.17
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.077
T
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.41
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.8
L
PrimateAI
Benign
0.25
T
PROVEAN
Pathogenic
-6.2
D
REVEL
Benign
0.12
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.018
D
Polyphen
1.0
D
Vest4
0.34
MutPred
0.53
Loss of glycosylation at S18 (P = 0.0947);
MVP
0.71
MPC
0.16
ClinPred
0.99
D
GERP RS
3.8
Varity_R
0.36
gMVP
0.20

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.

Other links and lift over

dbSNP: rs1173285720; hg19: chrX-130678108; API