chr6-29440427-C-T

Position:

• chr6-29440427-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.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. 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 0.024 (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

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=0.003257513).
• 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/exons	MANE	Protein	UniProt
OR10C1	NM_013941.4	c.412C>T	p.Arg138Trp	missense_variant	1/1	ENST00000444197.3	NP_039229.3
OR11A1	NM_001394828.1	c.-388-8440G>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.412C>T	p.Arg138Trp	missense_variant	1/1	6	NM_013941.4	ENSP00000419119.1
OR11A1	ENST00000377149.5	c.-388-8440G>A		intron_variant		6	NM_001394828.1	ENSP00000366354.1
OR10C1	ENST00000622521.1	c.418C>T	p.Arg140Trp	missense_variant	1/1	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

GnomAD3 exomes AF: 0.0104 AC: 2574 AN: 247268 Hom.: 50 AF XY: 0.00892 AC XY: 1200 AN XY: 134472

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 SAS exome AF: 0.00154

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

Gnomad4 AFR exome AF: 0.0745

Gnomad4 AMR exome AF: 0.0149

Gnomad4 ASJ exome AF: 0.0214

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00169

Gnomad4 FIN exome AF: 0.000357

Gnomad4 NFE exome AF: 0.00459

Gnomad4 OTH exome AF: 0.0115

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

Gnomad4 AFR AF: 0.0697

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00547

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.00877 Hom.: 25

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;.
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
Varity_R		0.16
gMVP		0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs17177646; hg19: chr6-29408204; COSMIC: COSV65823338;