11-59713496-A-G

Position:

• chr11-59713496-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001005324.1(OR10V1):​c.350T>C​(p.Val117Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0837 in 1,613,610 control chromosomes in the GnomAD database, including 11,134 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (4100 hom., cov: 31)
  • Exomes 𝑓: 0.075 (7034 hom.)
• Consequence: OR10V1 NM_001005324.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.57

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.18365E-4).
• BP6: Variant 11-59713496-A-G is Benign according to our data. Variant chr11-59713496-A-G is described in ClinVar as [Benign]. Clinvar id is 1247627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10V1	NM_001005324.1	c.350T>C	p.Val117Ala	missense_variant	1/1	ENST00000307552.3	NP_001005324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10V1	ENST00000307552.3	c.350T>C	p.Val117Ala	missense_variant	1/1	6	NM_001005324.1	ENSP00000302199.2
STX3	ENST00000641815	c.-535A>G		5_prime_UTR_premature_start_codon_gain_variant	1/12			ENSP00000493027.1
STX3	ENST00000641815	c.-535A>G		5_prime_UTR_variant	1/12			ENSP00000493027.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25939 AN: 152040 Hom.: 4066 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.0453

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.140

GnomAD3 exomes AF: 0.106 AC: 26444 AN: 250294 Hom.: 2643 AF XY: 0.0916 AC XY: 12390 AN XY: 135296

Gnomad AFR exome AF: 0.423

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.0330

Gnomad EAS exome AF: 0.0659

Gnomad SAS exome AF: 0.0472

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.0597

Gnomad OTH exome AF: 0.0747

GnomAD4 exome AF: 0.0746 AC: 109002 AN: 1461450 Hom.: 7034 Cov.: 34 AF XY: 0.0719 AC XY: 52262 AN XY: 727012

Gnomad4 AFR exome AF: 0.432

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.0331

Gnomad4 EAS exome AF: 0.0688

Gnomad4 SAS exome AF: 0.0471

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.0603

Gnomad4 OTH exome AF: 0.0828

GnomAD4 genome AF: 0.171 AC: 26035 AN: 152160 Hom.: 4100 Cov.: 31 AF XY: 0.170 AC XY: 12664 AN XY: 74408

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.0601

Gnomad4 SAS AF: 0.0449

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0586

Gnomad4 OTH AF: 0.139

Alfa AF: 0.0861 Hom.: 1606

Bravo AF: 0.189

TwinsUK AF: 0.0542 AC: 201

ALSPAC AF: 0.0581 AC: 224

ESP6500AA AF: 0.403 AC: 1772

ESP6500EA AF: 0.0616 AC: 529

ExAC AF: 0.104 AC: 12661

Asia WGS AF: 0.0970 AC: 338 AN: 3478

EpiCase AF: 0.0536

EpiControl AF: 0.0527

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	This variant is associated with the following publications: (PMID: 32583022) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.85
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.00042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	2.8	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.043
MPC		0.045
ClinPred		0.0034	T
GERP RS		4.4
Varity_R		0.024
gMVP		0.092

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

LitVar

Other links and lift over

dbSNP: rs472177; hg19: chr11-59480969; COSMIC: COSV55698271;