chr11-59504207-T-G

Variant summary

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

The NM_001004706.1(OR4D11):​c.632T>G​(p.Phe211Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

OR4D11
NM_001004706.1 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20
Variant links:
Genes affected
OR4D11 (HGNC:15174): (olfactory receptor family 4 subfamily D member 11) 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]

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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, 0.789

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR4D11NM_001004706.1 linkuse as main transcriptc.632T>G p.Phe211Cys missense_variant 1/1 ENST00000313253.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR4D11ENST00000313253.1 linkuse as main transcriptc.632T>G p.Phe211Cys missense_variant 1/1 NM_001004706.1 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

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 GeneticsMay 04, 2022The c.632T>G (p.F211C) alteration is located in exon 1 (coding exon 1) of the OR4D11 gene. This alteration results from a T to G substitution at nucleotide position 632, causing the phenylalanine (F) at amino acid position 211 to be replaced by a cysteine (C). 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
0.20
BayesDel_addAF
Uncertain
0.086
D
BayesDel_noAF
Benign
-0.11
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Benign
0.60
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.020
T
MetaRNN
Pathogenic
0.79
D
MetaSVM
Benign
-0.37
T
MutationAssessor
Uncertain
2.8
M
MutationTaster
Benign
0.90
D
PrimateAI
Benign
0.29
T
PROVEAN
Pathogenic
-7.6
D
REVEL
Uncertain
0.33
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.49
MutPred
0.70
Loss of stability (P = 0.1962);
MVP
0.69
MPC
0.091
ClinPred
1.0
D
GERP RS
5.4
Varity_R
0.87
gMVP
0.31

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-59271680; API