14-20224334-T-C

Variant names:

• chr14-20224334-T-C
• rs1594233873
• NM_001004480.1:c.625T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004480.1(OR11H6):​c.625T>C​(p.Ser209Pro) 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 benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR11H6 NM_001004480.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0390

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]

ACMG classification

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=0.02370885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR11H6	NM_001004480.1	c.625T>C	p.Ser209Pro	missense_variant	Exon 1 of 1	ENST00000315519.3	NP_001004480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR11H6	ENST00000315519.3	c.625T>C	p.Ser209Pro	missense_variant	Exon 1 of 1	6	NM_001004480.1	ENSP00000319071.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 25, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.9
DANN	Benign	0.14
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	4.2	N
REVEL	Benign	0.043
Sift	Benign	1.0	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.059
MutPred		0.42		Loss of catalytic residue at S209 (P = 0.0197);
MVP		0.14
MPC		0.070
ClinPred		0.044	T
GERP RS		2.9
Varity_R		0.058
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs1594233873; hg19: chr14-20692493;