12-55331707-C-T

Variant names:

• chr12-55331707-C-T
• NM_001388498.1:c.7C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001388498.1(OR6C3):​c.7C>T​(p.His3Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR6C3 NM_001388498.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.126

Genes affected

OR6C3 (HGNC:15437): (olfactory receptor family 6 subfamily C member 3) 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06059873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR6C3	NM_001388498.1	c.7C>T	p.His3Tyr	missense_variant	Exon 2 of 2	ENST00000641740.2	NP_001375427.1
OR6C3	NM_054104.2	c.7C>T	p.His3Tyr	missense_variant	Exon 2 of 2		NP_473445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR6C3	ENST00000641740.2	c.7C>T	p.His3Tyr	missense_variant	Exon 2 of 2		NM_001388498.1	ENSP00000493380.1
OR6C3	ENST00000641364.1	c.7C>T	p.His3Tyr	missense_variant	Exon 2 of 2			ENSP00000493034.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1453946 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 722778

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 31, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.7C>T (p.H3Y) alteration is located in exon 1 (coding exon 1) of the OR6C3 gene. This alteration results from a C to T substitution at nucleotide position 7, causing the histidine (H) at amino acid position 3 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.0
DANN	Benign	0.79
DEOGEN2	Benign	0.074	T;T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.26	.;.;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.061	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.67	N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.9	.;.;D
REVEL	Benign	0.10
Sift	Benign	0.18	.;.;T
Sift4G	Benign	0.30	.;.;T
Polyphen		0.0	B;B;B
Vest4		0.12
MutPred		0.39		Gain of catalytic residue at E8 (P = 0.0021);Gain of catalytic residue at E8 (P = 0.0021);Gain of catalytic residue at E8 (P = 0.0021);
MVP		0.43
MPC		0.0038
ClinPred		0.059	T
GERP RS		4.1
Varity_R		0.074
gMVP		0.067

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-55725491;