rs1325488934

Variant names:

• chr19-111124-C-T
• rs1325488934
• NM_001005240.3:c.446C>T

Variant summary

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

The NM_001005240.3(OR4F17):​c.446C>T​(p.Ser149Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4F17 NM_001005240.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67
• 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.446C>T	p.Ser149Leu	missense	Exon 3 of 3	NP_001005240.1	A0A126GWN0
	OR4F17	NM_001429985.1		c.509C>T	p.Ser170Leu	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.446C>T	p.Ser149Leu	missense	Exon 3 of 3	ENSP00000467301.1	Q8NGA8
	OR4F17	ENST00000618231.3	TSL:6	c.509C>T	p.Ser170Leu	missense	Exon 2 of 2	ENSP00000493422.2	A0A2U3U062
	OR4F17	ENST00000318050.4	TSL:6	c.446C>T	p.Ser149Leu	missense	Exon 1 of 1	ENSP00000315047.3	Q8NGA8

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150946 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: 0.0000296

Gnomad OTH AF: 0.000484

GnomAD2 exomes AF: 0.0000376 AC: 2 AN: 53136 AF XY: 0.0000374

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000974

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000269 AC: 37 AN: 1377064 Hom.: 0 Cov.: 27 AF XY: 0.0000277 AC XY: 19 AN XY: 686922

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

African (AFR) AF: 0.00 AC: 0 AN: 32540

American (AMR) AF: 0.0000689 AC: 3 AN: 43556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25286

East Asian (EAS) AF: 0.000129 AC: 5 AN: 38626

South Asian (SAS) AF: 0.0000724 AC: 6 AN: 82926

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4712

European-Non Finnish (NFE) AF: 0.0000164 AC: 17 AN: 1039232

Other (OTH) AF: 0.0000874 AC: 5 AN: 57238

⚠️ 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: 0.0000199 AC: 3 AN: 151066 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 73722

⚠️ 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: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5056

South Asian (SAS) AF: 0.00 AC: 0 AN: 4668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67534

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000744 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	0.48
BayesDel_addAF	Benign	0.0093	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.051
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.057	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0059	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.7
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.83	P
Vest4		0.61
MutPred		0.80		Gain of stability (P = 0.0636)
MVP		0.74
MPC		2.6
ClinPred		0.56	D
GERP RS		2.5
PromoterAI		0.0018	Neutral
Varity_R		0.53
gMVP		0.17
Mutation Taster		=99/1	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: rs1325488934; hg19: chr19-111124;