rs202070215

Variant names:

• chr11-59713521-C-A
• rs202070215
• NM_001005324.1:c.325G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-59713521-C-A
• chr11-59713521-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001005324.1(OR10V1):​c.325G>T​(p.Gly109Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G109S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR10V1 NM_001005324.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 0 publications found

Genes affected

OR10V1 (HGNC:15136): (olfactory receptor family 10 subfamily V 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]

STX3 (HGNC:11438): (syntaxin 3) The gene is a member of the syntaxin family. The encoded protein is targeted to the apical membrane of epithelial cells where it forms clusters and is important in establishing and maintaining polarity necessary for protein trafficking involving vesicle fusion and exocytosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

STX3 Gene-Disease associations (from GenCC):

• diarrhea 12, with microvillus atrophy

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• retinal dystrophy and microvillus inclusion disease

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• microvillus inclusion disease

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005324.1. 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
	OR10V1	NM_001005324.1	MANE Select	c.325G>T	p.Gly109Cys	missense	Exon 1 of 1	NP_001005324.1	Q8NGI7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10V1	ENST00000307552.3	TSL:6 MANE Select	c.325G>T	p.Gly109Cys	missense	Exon 1 of 1	ENSP00000302199.2	Q8NGI7
	STX3	ENST00000641815.1		c.-510C>A		5_prime_UTR	Exon 1 of 12	ENSP00000493027.1	A0A286YF28

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0048	T
Eigen	Uncertain	0.37
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.21	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.099
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.44		Gain of catalytic residue at G109 (P = 0.0351)
MVP		0.80
MPC		0.29
ClinPred		0.99	D
GERP RS		4.4
PromoterAI		-0.027	Neutral
Varity_R		0.86
gMVP		0.21
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: rs202070215; hg19: chr11-59480994;