chr19-15728570-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_013939.2(OR10H2):​c.527A>T​(p.His176Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,613,916 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000068 ( 1 hom. )

Consequence

OR10H2
NM_013939.2 missense

Scores

4
3
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.981
Variant links:
Genes affected
OR10H2 (HGNC:8173): (olfactory receptor family 10 subfamily H member 2) 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR10H2NM_013939.2 linkuse as main transcriptc.527A>T p.His176Leu missense_variant 1/1 ENST00000305899.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR10H2ENST00000305899.5 linkuse as main transcriptc.527A>T p.His176Leu missense_variant 1/1 NM_013939.2 P1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152130
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251390
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135860
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:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000704
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000677
AC:
99
AN:
1461786
Hom.:
1
Cov.:
37
AF XY:
0.0000633
AC XY:
46
AN XY:
727160
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000746
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152130
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000135
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 11, 2021The c.527A>T (p.H176L) alteration is located in exon 1 (coding exon 1) of the OR10H2 gene. This alteration results from a A to T substitution at nucleotide position 527, causing the histidine (H) at amino acid position 176 to be replaced by a leucine (L). 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
0.31
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
22
DANN
Benign
0.93
DEOGEN2
Benign
0.042
T
Eigen
Uncertain
0.32
Eigen_PC
Benign
0.086
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.0030
T
MetaRNN
Pathogenic
0.81
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.6
H
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.22
T
PROVEAN
Pathogenic
-11
D
REVEL
Benign
0.14
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.016
D
Polyphen
0.96
D
Vest4
0.52
MVP
0.49
MPC
1.1
ClinPred
0.99
D
GERP RS
3.4
Varity_R
0.76
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs774211140; hg19: chr19-15839380; API