chr6-29440376-C-T

Position:

• chr6-29440376-C-T

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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=0.016771823).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10C1	NM_013941.4	c.361C>T	p.Arg121Cys	missense_variant	1/1	ENST00000444197.3	NP_039229.3
OR11A1	NM_001394828.1	c.-388-8389G>A		intron_variant		ENST00000377149.5	NP_001381757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10C1	ENST00000444197.3	c.361C>T	p.Arg121Cys	missense_variant	1/1	6	NM_013941.4	ENSP00000419119.1
OR11A1	ENST00000377149.5	c.-388-8389G>A		intron_variant		6	NM_001394828.1	ENSP00000366354.1
OR10C1	ENST00000622521.1	c.367C>T	p.Arg123Cys	missense_variant	1/1	6		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

GnomAD3 exomes AF: 0.0133 AC: 3288 AN: 247838 Hom.: 61 AF XY: 0.0120 AC XY: 1614 AN XY: 134696

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 SAS exome AF: 0.0139

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

Gnomad4 AFR exome AF: 0.0810

Gnomad4 AMR exome AF: 0.0156

Gnomad4 ASJ exome AF: 0.0214

Gnomad4 EAS exome AF: 0.00398

Gnomad4 SAS exome AF: 0.0132

Gnomad4 FIN exome AF: 0.000412

Gnomad4 NFE exome AF: 0.00480

Gnomad4 OTH exome AF: 0.0143

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

Gnomad4 AFR AF: 0.0756

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.0112

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00565

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0107 Hom.: 38

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 v4.3

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;T
MetaSVM	Uncertain	-0.075	T
MutationAssessor	Uncertain	2.7	M;.
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
Varity_R		0.59
gMVP		0.60

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: rs17177639; hg19: chr6-29408153;