NM_013941.4:c.412C>T

Variant names:

• chr6-29440427-C-T
• rs17177646
• NM_013941.4:c.412C>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.412C>T​(p.Arg138Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00835 in 1,613,976 control chromosomes in the GnomAD database, including 240 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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: 𝑓 0.024 (99 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (141 hom.)
• Consequence: OR10C1 NM_013941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• 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=0.003257513).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10C1	NM_013941.4	c.412C>T	p.Arg138Trp	missense_variant	Exon 1 of 1	ENST00000444197.3	NP_039229.3
OR11A1	NM_001394828.1	c.-388-8440G>A		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.412C>T	p.Arg138Trp	missense_variant	Exon 1 of 1	6	NM_013941.4	ENSP00000419119.1
OR11A1	ENST00000377149.5	c.-388-8440G>A		intron_variant	Intron 1 of 4	6	NM_001394828.1	ENSP00000366354.1
OR10C1	ENST00000622521.1	c.418C>T	p.Arg140Trp	missense_variant	Exon 1 of 1	6		ENSP00000481429.1

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3639 AN: 152172 Hom.: 98 Cov.: 33

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00547

Gnomad OTH AF: 0.0301

GnomAD2 exomes AF: 0.0104 AC: 2574 AN: 247268 AF XY: 0.00892

Gnomad AFR exome AF: 0.0739

Gnomad AMR exome AF: 0.0136

Gnomad ASJ exome AF: 0.0206

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000463

Gnomad NFE exome AF: 0.00578

Gnomad OTH exome AF: 0.0122

GnomAD4 exome AF: 0.00673 AC: 9837 AN: 1461686 Hom.: 141 Cov.: 35 AF XY: 0.00646 AC XY: 4694 AN XY: 727150

African (AFR) AF: 0.0745 AC: 2493 AN: 33476

American (AMR) AF: 0.0149 AC: 667 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 558 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00169 AC: 146 AN: 86252

European-Finnish (FIN) AF: 0.000357 AC: 19 AN: 53272

Middle Eastern (MID) AF: 0.0260 AC: 150 AN: 5768

European-Non Finnish (NFE) AF: 0.00459 AC: 5106 AN: 1111974

Other (OTH) AF: 0.0115 AC: 696 AN: 60388

GnomAD4 genome AF: 0.0239 AC: 3644 AN: 152290 Hom.: 99 Cov.: 33 AF XY: 0.0225 AC XY: 1677 AN XY: 74474

African (AFR) AF: 0.0697 AC: 2893 AN: 41536

American (AMR) AF: 0.0148 AC: 227 AN: 15312

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

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

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00547 AC: 372 AN: 68020

Other (OTH) AF: 0.0298 AC: 63 AN: 2116

Alfa AF: 0.0119 Hom.: 58

Bravo AF: 0.0275

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.0746 AC: 225

ESP6500EA AF: 0.00720 AC: 39

ExAC AF: 0.0106 AC: 1273

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.00676

EpiControl AF: 0.00735

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0085	T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.030	N
MetaRNN	Benign	0.0033	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.
PhyloP100		-1.3
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-4.8	D;.
REVEL	Benign	0.073
Sift	Uncertain	0.0020	D;.
Polyphen		0.99	D;.
MPC		0.90
ClinPred		0.040	T
GERP RS		-1.2
PromoterAI		0.035	Neutral
Varity_R		0.16
gMVP		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17177646; hg19: chr6-29408204; COSMIC: COSV65823338;