6-29440493-C-T

Variant names:

• chr6-29440493-C-T
• rs2074468
• NM_013941.4:c.478C>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.478C>T​(p.Pro160Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0462 in 1,613,438 control chromosomes in the GnomAD database, including 3,732 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.098 (1346 hom., cov: 32)
  • Exomes 𝑓: 0.041 (2386 hom.)
• Consequence: OR10C1 NM_013941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81
• Publications: 11 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=0.0041463077).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10C1	NM_013941.4	MANE Select	c.478C>T	p.Pro160Ser	missense	Exon 1 of 1	NP_039229.3
	OR11A1	NM_001394828.1	MANE Select	c.-388-8506G>A		intron	N/A	NP_001381757.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10C1	ENST00000444197.3	TSL:6 MANE Select	c.478C>T	p.Pro160Ser	missense	Exon 1 of 1	ENSP00000419119.1
	OR11A1	ENST00000377149.5	TSL:6 MANE Select	c.-388-8506G>A		intron	N/A	ENSP00000366354.1
	OR10C1	ENST00000622521.1	TSL:6	c.484C>T	p.Pro162Ser	missense	Exon 1 of 1	ENSP00000481429.1

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 14822 AN: 152062 Hom.: 1336 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0923

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.0772

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.115

GnomAD2 exomes AF: 0.0552 AC: 13611 AN: 246696 AF XY: 0.0506

Gnomad AFR exome AF: 0.240

Gnomad AMR exome AF: 0.0692

Gnomad ASJ exome AF: 0.0938

Gnomad EAS exome AF: 0.0501

Gnomad FIN exome AF: 0.0209

Gnomad NFE exome AF: 0.0318

Gnomad OTH exome AF: 0.0585

GnomAD4 exome AF: 0.0409 AC: 59762 AN: 1461258 Hom.: 2386 Cov.: 35 AF XY: 0.0407 AC XY: 29593 AN XY: 726952

African (AFR) AF: 0.248 AC: 8308 AN: 33462

American (AMR) AF: 0.0730 AC: 3265 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0936 AC: 2446 AN: 26130

East Asian (EAS) AF: 0.0825 AC: 3275 AN: 39698

South Asian (SAS) AF: 0.0471 AC: 4066 AN: 86248

European-Finnish (FIN) AF: 0.0197 AC: 1045 AN: 53156

Middle Eastern (MID) AF: 0.111 AC: 639 AN: 5768

European-Non Finnish (NFE) AF: 0.0298 AC: 33116 AN: 1111692

Other (OTH) AF: 0.0597 AC: 3602 AN: 60382

GnomAD4 genome AF: 0.0976 AC: 14856 AN: 152180 Hom.: 1346 Cov.: 32 AF XY: 0.0945 AC XY: 7034 AN XY: 74408

African (AFR) AF: 0.235 AC: 9759 AN: 41468

American (AMR) AF: 0.0921 AC: 1409 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3472

East Asian (EAS) AF: 0.0766 AC: 396 AN: 5172

South Asian (SAS) AF: 0.0580 AC: 280 AN: 4830

European-Finnish (FIN) AF: 0.0180 AC: 191 AN: 10624

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0326 AC: 2215 AN: 67998

Other (OTH) AF: 0.114 AC: 240 AN: 2112

Alfa AF: 0.0414 Hom.: 627

Bravo AF: 0.110

TwinsUK AF: 0.0345 AC: 128

ALSPAC AF: 0.0293 AC: 113

ESP6500AA AF: 0.230 AC: 696

ESP6500EA AF: 0.0340 AC: 184

ExAC AF: 0.0551 AC: 6592

Asia WGS AF: 0.0760 AC: 265 AN: 3478

EpiCase AF: 0.0370

EpiControl AF: 0.0392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.016
DANN	Benign	0.64
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0071	N
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-2.8
PrimateAI	Benign	0.26	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.038
Sift	Benign	0.48	T
Polyphen		0.0	B
MPC		0.34
ClinPred		0.000017	T
GERP RS		0.87
Varity_R		0.038
gMVP		0.30
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2074468; hg19: chr6-29408270;