chr6-29440376-C-T

Variant names:

• chr6-29440376-C-T
• rs17177639
• NM_013941.4:c.361C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013941.4(OR10C1):​c.361C>T​(p.Arg121Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00975 in 1,614,030 control chromosomes in the GnomAD database, including 303 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.

• Frequency:
  • Genomes: 𝑓 0.027 (115 hom., cov: 32)
  • Exomes 𝑓: 0.0080 (188 hom.)
• Consequence: OR10C1 NM_013941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.704
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016771823).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013941.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10C1	NM_013941.4	MANE Select	c.361C>T	p.Arg121Cys	missense	Exon 1 of 1	NP_039229.3
	OR11A1	NM_001394828.1	MANE Select	c.-388-8389G>A		intron	N/A	NP_001381757.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10C1	ENST00000444197.3	TSL:6 MANE Select	c.361C>T	p.Arg121Cys	missense	Exon 1 of 1	ENSP00000419119.1
	OR11A1	ENST00000377149.5	TSL:6 MANE Select	c.-388-8389G>A		intron	N/A	ENSP00000366354.1
	OR10C1	ENST00000622521.1	TSL:6	c.367C>T	p.Arg123Cys	missense	Exon 1 of 1	ENSP00000481429.1

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4041 AN: 152186 Hom.: 115 Cov.: 32

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00564

Gnomad OTH AF: 0.0330

GnomAD2 exomes AF: 0.0133 AC: 3288 AN: 247838 AF XY: 0.0120

Gnomad AFR exome AF: 0.0801

Gnomad AMR exome AF: 0.0141

Gnomad ASJ exome AF: 0.0206

Gnomad EAS exome AF: 0.00879

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.00614

Gnomad OTH exome AF: 0.0138

GnomAD4 exome AF: 0.00800 AC: 11694 AN: 1461726 Hom.: 188 Cov.: 35 AF XY: 0.00796 AC XY: 5791 AN XY: 727166

African (AFR) AF: 0.0810 AC: 2710 AN: 33468

American (AMR) AF: 0.0156 AC: 697 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 558 AN: 26134

East Asian (EAS) AF: 0.00398 AC: 158 AN: 39698

South Asian (SAS) AF: 0.0132 AC: 1140 AN: 86256

European-Finnish (FIN) AF: 0.000412 AC: 22 AN: 53344

Middle Eastern (MID) AF: 0.0354 AC: 204 AN: 5768

European-Non Finnish (NFE) AF: 0.00480 AC: 5339 AN: 1111940

Other (OTH) AF: 0.0143 AC: 866 AN: 60394

GnomAD4 genome AF: 0.0266 AC: 4047 AN: 152304 Hom.: 115 Cov.: 32 AF XY: 0.0253 AC XY: 1882 AN XY: 74480

African (AFR) AF: 0.0756 AC: 3141 AN: 41546

American (AMR) AF: 0.0156 AC: 239 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3472

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5180

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00565 AC: 384 AN: 68022

Other (OTH) AF: 0.0326 AC: 69 AN: 2116

Alfa AF: 0.0147 Hom.: 101

Bravo AF: 0.0299

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.0785 AC: 237

ESP6500EA AF: 0.00720 AC: 39

ExAC AF: 0.0137 AC: 1660

Asia WGS AF: 0.0220 AC: 77 AN: 3478

EpiCase AF: 0.00714

EpiControl AF: 0.00788

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.0018
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.58	D
MetaRNN	Benign	0.017	T
MetaSVM	Uncertain	-0.075	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.70
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0070	D
Polyphen		0.77	P
MPC		1.3
ClinPred		0.041	T
GERP RS		3.1
PromoterAI		-0.010	Neutral
Varity_R		0.59
gMVP		0.60
Mutation Taster		=92/8	polymorphism (auto)

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: rs17177639; hg19: chr6-29408153;