12-55452500-C-A

Position:

• chr12-55452500-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_054105.2(OR6C2):​c.287C>A​(p.Ala96Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR6C2 NM_054105.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.760

Genes affected

OR6C2 (HGNC:15436): (olfactory receptor family 6 subfamily C member 2) 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]

LOC124902940 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16143867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR6C2	NM_054105.2	c.287C>A	p.Ala96Asp	missense_variant	2/2	ENST00000641202.1	NP_473446.1
LOC124902940	XR_007063324.1	n.74G>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6C2	ENST00000641202.1	c.287C>A	p.Ala96Asp	missense_variant	2/2		NM_054105.2	ENSP00000493222.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.287C>A (p.A96D) alteration is located in exon 1 (coding exon 1) of the OR6C2 gene. This alteration results from a C to A substitution at nucleotide position 287, causing the alanine (A) at amino acid position 96 to be replaced by an aspartic acid (D). 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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T;T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.11	N
LIST_S2	Uncertain	0.92	.;.;D
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	M;M;M
PrimateAI	Benign	0.18	T
PROVEAN	Uncertain	-3.4	.;.;D
REVEL	Benign	0.20
Sift	Benign	0.063	.;.;T
Sift4G	Benign	0.20	.;.;T
Polyphen		0.66	P;P;P
Vest4		0.56
MutPred		0.35		Gain of relative solvent accessibility (P = 0.2363);Gain of relative solvent accessibility (P = 0.2363);Gain of relative solvent accessibility (P = 0.2363);
MVP		0.67
MPC		0.0040
ClinPred		0.90	D
GERP RS		0.43
Varity_R		0.62
gMVP		0.30

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: chr12-55846284;