chr6-29440193-T-A

Variant names:

• chr6-29440193-T-A
• rs2074469
• NM_013941.4:c.178T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013941.4(OR10C1):​c.178T>A​(p.Phe60Ile) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR10C1 NM_013941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.767
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3453821).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10C1	NM_013941.4	c.178T>A	p.Phe60Ile	missense_variant	Exon 1 of 1	ENST00000444197.3	NP_039229.3
OR11A1	NM_001394828.1	c.-388-8206A>T		intron_variant	Intron 1 of 4	ENST00000377149.5	NP_001381757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR10C1	ENST00000444197.3	c.178T>A	p.Phe60Ile	missense_variant	Exon 1 of 1	6	NM_013941.4	ENSP00000419119.1
OR11A1	ENST00000377149.5	c.-388-8206A>T		intron_variant	Intron 1 of 4	6	NM_001394828.1	ENSP00000366354.1
OR10C1	ENST00000622521.1	c.184T>A	p.Phe62Ile	missense_variant	Exon 1 of 1	6		ENSP00000481429.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;.
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.56	D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.2	M;.
PhyloP100		0.77
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-5.4	D;.
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;.
Polyphen		1.0	D;.
MutPred		0.48		Gain of catalytic residue at L65 (P = 0.0486);.;
MVP		0.14
MPC		1.3
ClinPred		0.91	D
GERP RS		3.6
PromoterAI		-0.017	Neutral
Varity_R		0.78
gMVP		0.39
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs2074469; hg19: chr6-29407970;