chr6-29440233-C-A

Position:

• chr6-29440233-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013941.4(OR10C1):​c.218C>A​(p.Thr73Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR10C1 NM_013941.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.767

Genes affected

OR10C1 (HGNC:8165): (olfactory receptor family 10 subfamily C 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]

OR11A1 (HGNC:8176): (olfactory receptor family 11 subfamily A 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10C1	NM_013941.4	c.218C>A	p.Thr73Lys	missense_variant	1/1	ENST00000444197.3	NP_039229.3
OR11A1	NM_001394828.1	c.-388-8246G>T		intron_variant		ENST00000377149.5	NP_001381757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10C1	ENST00000444197.3	c.218C>A	p.Thr73Lys	missense_variant	1/1		NM_013941.4	ENSP00000419119	P1
OR11A1	ENST00000377149.5	c.-388-8246G>T		intron_variant			NM_001394828.1	ENSP00000366354	P1
OR10C1	ENST00000622521.1	c.224C>A	p.Thr75Lys	missense_variant	1/1			ENSP00000481429

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.218C>A (p.T73K) alteration is located in exon 1 (coding exon 1) of the OR10C1 gene. This alteration results from a C to A substitution at nucleotide position 218, causing the threonine (T) at amino acid position 73 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	Pathogenic	0.71
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.023	T;.
Eigen	Benign	0.0079
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.057	N
M_CAP	Benign	0.0018	T
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.8	H;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.5	D;.
REVEL	Benign	0.13
Sift	Uncertain	0.011	D;.
Polyphen		0.97	D;.
MutPred		0.76		Gain of ubiquitination at T73 (P = 0.0177);.;
MVP		0.095
MPC		0.54
ClinPred		0.74	D
GERP RS		3.5
Varity_R		0.78
gMVP		0.81

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: rs1252276618; hg19: chr6-29408010;