19-111142-T-C

Variant names:

• chr19-111142-T-C
• rs1968706025
• NM_001005240.3:c.464T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001005240.3(OR4F17):​c.464T>C​(p.Phe155Ser) 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 0.0 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F17 NM_001005240.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.58
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.776

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005240.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4F17	NM_001005240.3	MANE Select	c.464T>C	p.Phe155Ser	missense	Exon 3 of 3	NP_001005240.1	A0A126GWN0
	OR4F17	NM_001429985.1		c.527T>C	p.Phe176Ser	missense	Exon 2 of 2	NP_001416914.1	A0A2U3U062

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4F17	ENST00000585993.3	TSL:6 MANE Select	c.464T>C	p.Phe155Ser	missense	Exon 3 of 3	ENSP00000467301.1	Q8NGA8
	OR4F17	ENST00000618231.3	TSL:6	c.527T>C	p.Phe176Ser	missense	Exon 2 of 2	ENSP00000493422.2	A0A2U3U062
	OR4F17	ENST00000318050.4	TSL:6	c.464T>C	p.Phe155Ser	missense	Exon 1 of 1	ENSP00000315047.3	Q8NGA8

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150872 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1425288 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 708866

African (AFR) AF: 0.00 AC: 0 AN: 33084

American (AMR) AF: 0.00 AC: 0 AN: 44116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25766

East Asian (EAS) AF: 0.00 AC: 0 AN: 39048

South Asian (SAS) AF: 0.00 AC: 0 AN: 84670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4962

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081494

Other (OTH) AF: 0.00 AC: 0 AN: 58962

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 150872 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 73542

African (AFR) AF: 0.00 AC: 0 AN: 41376

American (AMR) AF: 0.00 AC: 0 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5068

South Asian (SAS) AF: 0.00 AC: 0 AN: 4670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67448

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.055
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0019	T
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.72		Loss of catalytic residue at F155 (P = 0.0076)
MVP		0.67
MPC		5.0
ClinPred		1.0	D
GERP RS		2.5
PromoterAI		-0.0072	Neutral
Varity_R		0.78
gMVP		0.094
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1968706025; hg19: chr19-111142;