Genetic Variant NM_001005518.1:c.152T>C (chr12-55400680-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005518.1(OR6C65):c.152T>C(p.Ile51Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 1,603,852 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

OR6C65
NM_001005518.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.64

Publications

1 publications found

Variant links:

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]

OR6C65 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020296574).

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.152T>C	p.Ile51Thr	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.152T>C	p.Ile51Thr	missense	Exon 1 of 1	ENSP00000368986.2	A6NJZ3

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000402

AC:

AN:

248796

AF XY:

0.0000223

show subpopulations

Gnomad AFR exome

AF:

0.000557

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1451532

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

722230

show subpopulations

African (AFR)

AF:

0.000512

AC:

AN:

33216

American (AMR)

AF:

0.0000225

AC:

AN:

44412

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26034

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.00

AC:

AN:

85600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103618

Other (OTH)

AF:

0.0000167

AC:

AN:

60014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000131

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000457

AC:

AN:

41568

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000989

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.28

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.0018

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0084

LIST_S2

Benign

0.47

M_CAP

Benign

0.0015

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-1.1

PhyloP100

-1.6

PrimateAI

Benign

0.19

PROVEAN

Benign

1.8

REVEL

Benign

0.037

Sift

Benign

0.11

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.053

MVP

0.014

MPC

0.023

ClinPred

0.031

GERP RS

-6.0

PromoterAI

-0.0033

Neutral

(source)

Varity_R

0.041

gMVP

0.032

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over