chr6-131701185-C-G

Position:

• chr6-131701185-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_030908.2(OR2A4):​c.217G>C​(p.Ala73Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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: 11)
  • Exomes 𝑓: 0.0000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2A4 NM_030908.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.79

Genes affected

OR2A4 (HGNC:14729): (olfactory receptor family 2 subfamily A member 4) 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]

ENPP3 (HGNC:3358): (ectonucleotide pyrophosphatase/phosphodiesterase 3) The protein encoded by this gene belongs to a series of ectoenzymes that are involved in hydrolysis of extracellular nucleotides. These ectoenzymes possess ATPase and ATP pyrophosphatase activities and are type II transmembrane proteins. Expression of the related rat mRNA has been found in a subset of immature glial cells and in the alimentary tract. The corresponding rat protein has been detected in the pancreas, small intestine, colon, and liver. The human mRNA is expressed in glioma cells, prostate, and uterus. Expression of the human protein has been detected in uterus, basophils, and mast cells. Two transcript variants, one protein coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Oct 2015]

ENPP3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2108745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2A4	NM_030908.2	c.217G>C	p.Ala73Pro	missense_variant	1/1	ENST00000315453.4	NP_112170.1
ENPP3	NM_005021.5	c.1412+7561C>G		intron_variant		ENST00000357639.8	NP_005012.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2A4	ENST00000315453.4	c.217G>C	p.Ala73Pro	missense_variant	1/1	6	NM_030908.2	ENSP00000319546.2
ENPP3	ENST00000357639.8	c.1412+7561C>G		intron_variant		1	NM_005021.5	ENSP00000350265.3
ENPP3	ENST00000414305.5	c.1412+7561C>G		intron_variant		1		ENSP00000406261.1
ENPP3	ENST00000358229.6	c.1412+7561C>G		intron_variant		1		ENSP00000350964.5

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000237 AC: 2 AN: 845560 Hom.: 0 Cov.: 11 AF XY: 0.00000228 AC XY: 1 AN XY: 439004

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: 0.00000350

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 11

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

Sep 27, 2024

The c.217G>C (p.A73P) alteration is located in exon 1 (coding exon 1) of the OR2A4 gene. This alteration results from a G to C substitution at nucleotide position 217, causing the alanine (A) at amino acid position 73 to be replaced by a proline (P). 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	0.17
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.3	L
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.085
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.23
MutPred		0.58		Loss of helix (P = 0.2271);
MVP		0.49
ClinPred		0.60	D
GERP RS		0.69
Varity_R		0.67
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-132022325;