19-110890-C-A

Variant names:

• chr19-110890-C-A
• NM_001005240.3:c.212C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001005240.3(OR4F17):​c.212C>A​(p.Ala71Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A71V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000060 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F17 NM_001005240.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0500

Genes affected

OR4F17 (HGNC:15381): (olfactory receptor family 4 subfamily F member 17) 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34613514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4F17	NM_001005240.3	c.212C>A	p.Ala71Asp	missense_variant	Exon 3 of 3	ENST00000585993.3	NP_001005240.1
OR4F17	NM_001429985.1	c.275C>A	p.Ala92Asp	missense_variant	Exon 2 of 2		NP_001416914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4F17	ENST00000585993.3	c.212C>A	p.Ala71Asp	missense_variant	Exon 3 of 3	6	NM_001005240.3	ENSP00000467301.1
OR4F17	ENST00000618231.3	c.275C>A	p.Ala92Asp	missense_variant	Exon 2 of 2	6		ENSP00000493422.2
OR4F17	ENST00000318050.4	c.212C>A	p.Ala71Asp	missense_variant	Exon 1 of 1	6		ENSP00000315047.3
OR4F17	ENST00000641591.1	n.194+209C>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000598 AC: 8 AN: 1337558 Hom.: 0 Cov.: 25 AF XY: 0.00000447 AC XY: 3 AN XY: 670808

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: 0.00000798

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.212C>A (p.A71D) alteration is located in exon 1 (coding exon 1) of the OR4F17 gene. This alteration results from a C to A substitution at nucleotide position 212, causing the alanine (A) at amino acid position 71 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	0.80
BayesDel_addAF	Benign	0.0011	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T;.;T
Eigen	Benign	-0.0091
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.57	.;T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.6	.;.;D
REVEL	Benign	0.20
Sift	Uncertain	0.0010	.;.;D
Sift4G	Pathogenic	0.0010	D;.;D
Polyphen		1.0	D;.;D
Vest4		0.60
MutPred		0.75		Gain of disorder (P = 0.0324);.;Gain of disorder (P = 0.0324);
MVP		0.72
MPC		4.6
ClinPred		0.96	D
GERP RS		1.2
Varity_R		0.65
gMVP		0.27

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: chr19-110890;