14-20223939-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004480.1(OR11H6):​c.230T>A​(p.Met77Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000124 in 1,614,148 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000072 ( 1 hom. )

Consequence

OR11H6
NM_001004480.1 missense

Scores

7
4
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08
Variant links:
Genes affected
OR11H6 (HGNC:15349): (olfactory receptor family 11 subfamily H member 6) 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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.070957094).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR11H6NM_001004480.1 linkuse as main transcriptc.230T>A p.Met77Lys missense_variant 1/1 ENST00000315519.3 NP_001004480.1 Q8NGC7A0A126GVP4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR11H6ENST00000315519.3 linkuse as main transcriptc.230T>A p.Met77Lys missense_variant 1/16 NM_001004480.1 ENSP00000319071.2 Q8NGC7

Frequencies

GnomAD3 genomes
AF:
0.000618
AC:
94
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00212
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.0000147
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000211
AC:
53
AN:
251334
Hom.:
0
AF XY:
0.000155
AC XY:
21
AN XY:
135832
show subpopulations
Gnomad AFR exome
AF:
0.00271
Gnomad AMR exome
AF:
0.000231
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000718
AC:
105
AN:
1461836
Hom.:
1
Cov.:
33
AF XY:
0.0000550
AC XY:
40
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00260
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.000624
AC:
95
AN:
152312
Hom.:
0
Cov.:
32
AF XY:
0.000537
AC XY:
40
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00214
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.0000272
Hom.:
0
Bravo
AF:
0.000771
ESP6500AA
AF:
0.00204
AC:
9
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000231
AC:
28

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 18, 2021The c.230T>A (p.M77K) alteration is located in exon 1 (coding exon 1) of the OR11H6 gene. This alteration results from a T to A substitution at nucleotide position 230, causing the methionine (M) at amino acid position 77 to be replaced by a lysine (K). 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
Uncertain
0.41
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.033
T
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.071
T
MetaSVM
Benign
-0.55
T
MutationAssessor
Pathogenic
3.0
M
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-5.9
D
REVEL
Uncertain
0.32
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.76
MVP
0.62
MPC
0.40
ClinPred
0.21
T
GERP RS
4.8
Varity_R
0.96
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs145052055; hg19: chr14-20692098; API