chr19-14828075-T-G

Position:

• chr19-14828075-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_017506.2(OR7A5):​c.167A>C​(p.His56Pro) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0026 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR7A5 NM_017506.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08

Genes affected

OR7A5 (HGNC:8368): (olfactory receptor family 7 subfamily A member 5) 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]

OR7C1 (HGNC:8373): (olfactory receptor family 7 subfamily C member 1) 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 Uncertain_significance. Variant got 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR7A5	NM_017506.2	c.167A>C	p.His56Pro	missense_variant	2/2	ENST00000322301.5
OR7C1	NM_001370485.4	c.-623+6999A>C		intron_variant		ENST00000641666.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR7A5	ENST00000322301.5	c.167A>C	p.His56Pro	missense_variant	2/2		NM_017506.2	P1
OR7C1	ENST00000641666.2	c.-623+6999A>C		intron_variant			NM_001370485.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 12 AN: 151878 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00257 AC: 3736 AN: 1451756 Hom.: 0 Cov.: 34 AF XY: 0.00237 AC XY: 1715 AN XY: 722436

Gnomad4 AFR exome AF: 0.00198

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00138

Gnomad4 EAS exome AF: 0.000911

Gnomad4 SAS exome AF: 0.000813

Gnomad4 FIN exome AF: 0.000432

Gnomad4 NFE exome AF: 0.00303

Gnomad4 OTH exome AF: 0.00245

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000724 AC: 11 AN: 151994 Hom.: 0 Cov.: 31 AF XY: 0.0000942 AC XY: 7 AN XY: 74288

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.0000946

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00

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

Nov 21, 2022

The c.167A>C (p.H56P) alteration is located in exon 1 (coding exon 1) of the OR7A5 gene. This alteration results from a A to C substitution at nucleotide position 167, causing the histidine (H) at amino acid position 56 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	0.25
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.019	T;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.61	.;T
M_CAP	Benign	0.0021	T
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Pathogenic	4.0	H;H
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-8.3	D;.
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.50
MutPred		0.71		Gain of glycosylation at T57 (P = 0.0584);Gain of glycosylation at T57 (P = 0.0584);
MVP		0.69
MPC		0.41
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.74
gMVP		0.57

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

LitVar

Other links and lift over

dbSNP: rs2044791373; hg19: chr19-14938887;