chr11-56290474-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005199.2(OR8H1):​c.589A>T​(p.Met197Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

OR8H1
NM_001005199.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.99
Variant links:
Genes affected
OR8H1 (HGNC:14824): (olfactory receptor family 8 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.02529928).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR8H1NM_001005199.2 linkuse as main transcriptc.589A>T p.Met197Leu missense_variant 2/2 ENST00000641600.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR8H1ENST00000641600.1 linkuse as main transcriptc.589A>T p.Met197Leu missense_variant 2/2 NM_001005199.2 P1
OR8H1ENST00000313022.2 linkuse as main transcriptc.589A>T p.Met197Leu missense_variant 1/1 P1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000313
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251322
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135816
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461866
Hom.:
0
Cov.:
33
AF XY:
0.00000550
AC XY:
4
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.0000224
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000919
AC:
14
AN:
152346
Hom.:
0
Cov.:
33
AF XY:
0.0000940
AC XY:
7
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000128
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5

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 GeneticsApr 04, 2024The c.589A>T (p.M197L) alteration is located in exon 1 (coding exon 1) of the OR8H1 gene. This alteration results from a A to T substitution at nucleotide position 589, causing the methionine (M) at amino acid position 197 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
0.096
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
0.36
DANN
Benign
0.33
DEOGEN2
Benign
0.0042
T;T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.026
.;T;T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.025
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.51
N;N;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.18
T
PROVEAN
Benign
0.36
.;N;.
REVEL
Benign
0.064
Sift
Benign
0.59
.;T;.
Sift4G
Benign
0.67
.;T;T
Polyphen
0.0
B;B;.
Vest4
0.099
MutPred
0.26
Gain of catalytic residue at M197 (P = 0.0041);Gain of catalytic residue at M197 (P = 0.0041);.;
MVP
0.20
MPC
0.018
ClinPred
0.020
T
GERP RS
2.5
Varity_R
0.068
gMVP
0.14

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: rs139901573; hg19: chr11-56057950; API