chr6-29440193-T-C

Position:

• chr6-29440193-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013941.4(OR10C1):​c.178T>C​(p.Phe60Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,613,666 control chromosomes in the GnomAD database, including 28,981 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2223 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26758 hom.)
• Consequence: OR10C1 NM_013941.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037362874).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10C1	NM_013941.4	c.178T>C	p.Phe60Leu	missense_variant	1/1	ENST00000444197.3	NP_039229.3
OR11A1	NM_001394828.1	c.-388-8206A>G		intron_variant		ENST00000377149.5	NP_001381757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10C1	ENST00000444197.3	c.178T>C	p.Phe60Leu	missense_variant	1/1		NM_013941.4	ENSP00000419119	P1
OR11A1	ENST00000377149.5	c.-388-8206A>G		intron_variant			NM_001394828.1	ENSP00000366354	P1
OR10C1	ENST00000622521.1	c.184T>C	p.Phe62Leu	missense_variant	1/1			ENSP00000481429

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24821 AN: 152020 Hom.: 2218 Cov.: 32

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.194 AC: 47950 AN: 247058 Hom.: 5035 AF XY: 0.191 AC XY: 25706 AN XY: 134480

Gnomad AFR exome AF: 0.0846

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.226

Gnomad SAS exome AF: 0.163

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.192

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.188 AC: 275484 AN: 1461528 Hom.: 26758 Cov.: 35 AF XY: 0.188 AC XY: 136794 AN XY: 727076

Gnomad4 AFR exome AF: 0.0820

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.163 AC: 24831 AN: 152138 Hom.: 2223 Cov.: 32 AF XY: 0.164 AC XY: 12216 AN XY: 74380

Gnomad4 AFR AF: 0.0876

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.166

Alfa AF: 0.187 Hom.: 5672

Bravo AF: 0.167

TwinsUK AF: 0.187 AC: 693

ALSPAC AF: 0.194 AC: 748

ESP6500AA AF: 0.0834 AC: 252

ESP6500EA AF: 0.188 AC: 1017

ExAC AF: 0.187 AC: 22355

Asia WGS AF: 0.156 AC: 542 AN: 3478

EpiCase AF: 0.188

EpiControl AF: 0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T;.
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.085
FATHMM_MKL	Benign	0.47	N
MetaRNN	Benign	0.0037	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	0.81	P;P;P
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.3	D;.
REVEL	Benign	0.13
Sift	Benign	0.068	T;.
Polyphen		1.0	D;.
MutPred		0.47		Loss of methylation at R63 (P = 0.1183);.;
MPC		1.2
ClinPred		0.022	T
GERP RS		3.6
Varity_R		0.54
gMVP		0.24

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: rs2074469; hg19: chr6-29407970; COSMIC: COSV65822234;