chr19-110893-C-T

Variant names:

• chr19-110893-C-T
• rs201438338
• NM_001005240.3:c.215C>T

Variant summary

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

The NM_001005240.3(OR4F17):​c.215C>T​(p.Pro72Leu) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000035 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000083 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F17 NM_001005240.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.71
• 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 0 ACMG points.

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.215C>T	p.Pro72Leu	missense	Exon 3 of 3	NP_001005240.1	A0A126GWN0
	OR4F17	NM_001429985.1		c.278C>T	p.Pro93Leu	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.215C>T	p.Pro72Leu	missense	Exon 3 of 3	ENSP00000467301.1	Q8NGA8
	OR4F17	ENST00000618231.3	TSL:6	c.278C>T	p.Pro93Leu	missense	Exon 2 of 2	ENSP00000493422.2	A0A2U3U062
	OR4F17	ENST00000318050.4	TSL:6	c.215C>T	p.Pro72Leu	missense	Exon 1 of 1	ENSP00000315047.3	Q8NGA8

Frequencies

GnomAD3 genomes AF: 0.0000349 AC: 5 AN: 143294 Hom.: 0 Cov.: 25

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: 0.0000772

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000825 AC: 11 AN: 1332806 Hom.: 0 Cov.: 25 AF XY: 0.00000897 AC XY: 6 AN XY: 668698

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000315 AC: 1 AN: 31716

American (AMR) AF: 0.00 AC: 0 AN: 44204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25458

East Asian (EAS) AF: 0.00 AC: 0 AN: 38228

South Asian (SAS) AF: 0.00 AC: 0 AN: 82174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3942

European-Non Finnish (NFE) AF: 0.0000100 AC: 10 AN: 997948

Other (OTH) AF: 0.00 AC: 0 AN: 55800

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000349 AC: 5 AN: 143294 Hom.: 0 Cov.: 25 AF XY: 0.0000145 AC XY: 1 AN XY: 69064

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40006

American (AMR) AF: 0.00 AC: 0 AN: 13860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3360

East Asian (EAS) AF: 0.00 AC: 0 AN: 4502

South Asian (SAS) AF: 0.00 AC: 0 AN: 4024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000772 AC: 5 AN: 64750

Other (OTH) AF: 0.00 AC: 0 AN: 1902

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000101646), which strongly suggests a high chance of mosaicism in these individuals.

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	0.52
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0048	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		3.7
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-9.7	D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.62		Gain of ubiquitination at K73 (P = 0.0898)
MVP		0.79
MPC		3.4
ClinPred		1.0	D
GERP RS		2.4
PromoterAI		0.015	Neutral
Varity_R		0.73
gMVP		0.16
Mutation Taster		=95/5	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: rs201438338; hg19: chr19-110893;