6-29440944-T-G

Position:

• chr6-29440944-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013941.4(OR10C1):​c.929T>G​(p.Met310Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00777 in 1,604,758 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.021 (65 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (120 hom.)
• Consequence: OR10C1 NM_013941.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.654

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003185898).
• BP6: Variant 6-29440944-T-G is Benign according to our data. Variant chr6-29440944-T-G is described in ClinVar as [Benign]. Clinvar id is 780982.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10C1	NM_013941.4	c.929T>G	p.Met310Arg	missense_variant	1/1	ENST00000444197.3	NP_039229.3
OR11A1	NM_001394828.1	c.-388-8957A>C		intron_variant		ENST00000377149.5	NP_001381757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10C1	ENST00000444197.3	c.929T>G	p.Met310Arg	missense_variant	1/1	6	NM_013941.4	ENSP00000419119.1
OR11A1	ENST00000377149.5	c.-388-8957A>C		intron_variant		6	NM_001394828.1	ENSP00000366354.1
OR10C1	ENST00000622521.1	c.935T>G	p.Met312Arg	missense_variant	1/1	6		ENSP00000481429.1

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3149 AN: 152070 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00546

Gnomad OTH AF: 0.0245

GnomAD3 exomes AF: 0.00967 AC: 2340 AN: 241976 Hom.: 39 AF XY: 0.00840 AC XY: 1109 AN XY: 132026

Gnomad AFR exome AF: 0.0636

Gnomad AMR exome AF: 0.0123

Gnomad ASJ exome AF: 0.0207

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00155

Gnomad FIN exome AF: 0.000516

Gnomad NFE exome AF: 0.00581

Gnomad OTH exome AF: 0.0113

GnomAD4 exome AF: 0.00641 AC: 9314 AN: 1452570 Hom.: 120 Cov.: 31 AF XY: 0.00621 AC XY: 4493 AN XY: 723026

Gnomad4 AFR exome AF: 0.0639

Gnomad4 AMR exome AF: 0.0134

Gnomad4 ASJ exome AF: 0.0213

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00168

Gnomad4 FIN exome AF: 0.000403

Gnomad4 NFE exome AF: 0.00458

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.0207 AC: 3156 AN: 152188 Hom.: 65 Cov.: 32 AF XY: 0.0194 AC XY: 1446 AN XY: 74416

Gnomad4 AFR AF: 0.0587

Gnomad4 AMR AF: 0.0135

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.00546

Gnomad4 OTH AF: 0.0242

Alfa AF: 0.00743 Hom.: 13

Bravo AF: 0.0237

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.0603 AC: 182

ESP6500EA AF: 0.00720 AC: 39

ExAC AF: 0.00969 AC: 1151

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.00676

EpiControl AF: 0.00717

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.0
DANN	Benign	0.56
DEOGEN2	Benign	0.0020	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.030	N
MetaRNN	Benign	0.0032	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.30	N;.
REVEL	Benign	0.028
Sift	Benign	0.11	T;.
Polyphen		0.012	B;.
MVP		0.014
MPC		0.52
ClinPred		0.00030	T
GERP RS		0.082
Varity_R		0.17
gMVP		0.28

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: rs11968123; hg19: chr6-29408721;