12-55400791-C-A

Variant names:

• chr12-55400791-C-A
• rs144035879
• NM_001005518.1:c.263C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001005518.1(OR6C65):​c.263C>A​(p.Thr88Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,612,954 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00083 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (1 hom.)
• Consequence: OR6C65 NM_001005518.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.08
• Publications: 6 publications found

Genes affected

OR6C65 (HGNC:31295): (olfactory receptor family 6 subfamily C member 65) 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00903663).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005518.1. 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
	OR6C65	NM_001005518.1	MANE Select	c.263C>A	p.Thr88Lys	missense	Exon 1 of 1	NP_001005518.1	A6NJZ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6C65	ENST00000379665.3	TSL:6 MANE Select	c.263C>A	p.Thr88Lys	missense	Exon 1 of 1	ENSP00000368986.2	A6NJZ3

Frequencies

GnomAD3 genomes AF: 0.000828 AC: 126 AN: 152182 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00117 AC: 294 AN: 250480 AF XY: 0.00134

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00183

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000469

Gnomad NFE exome AF: 0.00155

Gnomad OTH exome AF: 0.00246

GnomAD4 exome AF: 0.00103 AC: 1498 AN: 1460654 Hom.: 1 Cov.: 32 AF XY: 0.00109 AC XY: 795 AN XY: 726708

African (AFR) AF: 0.000209 AC: 7 AN: 33464

American (AMR) AF: 0.00170 AC: 76 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.000842 AC: 22 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000998 AC: 86 AN: 86186

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52908

Middle Eastern (MID) AF: 0.00329 AC: 19 AN: 5768

European-Non Finnish (NFE) AF: 0.00109 AC: 1217 AN: 1111444

Other (OTH) AF: 0.00116 AC: 70 AN: 60370

GnomAD4 genome AF: 0.000834 AC: 127 AN: 152300 Hom.: 2 Cov.: 32 AF XY: 0.000644 AC XY: 48 AN XY: 74486

African (AFR) AF: 0.000217 AC: 9 AN: 41550

American (AMR) AF: 0.00124 AC: 19 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00126 AC: 86 AN: 68028

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00146 Hom.: 0

Bravo AF: 0.00106

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.00131 AC: 159

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0010
DANN	Benign	0.75
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.0090	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.3	N
PhyloP100		-1.1
PrimateAI	Benign	0.19	T
PROVEAN	Benign	3.9	N
REVEL	Benign	0.085
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.048
MVP		0.014
MPC		0.023
ClinPred		0.011	T
GERP RS		-4.9
PromoterAI		0.0022	Neutral
Varity_R		0.026
gMVP		0.085
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs144035879; hg19: chr12-55794575;