NM_000916.4:c.1015G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000916.4(OXTR):c.1015G>A(p.Glu339Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,060 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

OXTR
NM_000916.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 7.84

Variant links:

Genes affected

OXTR (HGNC:8529): (oxytocin receptor) The protein encoded by this gene belongs to the G-protein coupled receptor family and acts as a receptor for oxytocin. Its activity is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. The oxytocin-oxytocin receptor system plays an important role in the uterus during parturition. [provided by RefSeq, Jul 2008]

OXTR links:

CAV3 (HGNC:1529): (caveolin 3) This gene encodes a caveolin family member, which functions as a component of the caveolae plasma membranes found in most cell types. Caveolin proteins are proposed to be scaffolding proteins for organizing and concentrating certain caveolin-interacting molecules. Mutations identified in this gene lead to interference with protein oligomerization or intra-cellular routing, disrupting caveolae formation and resulting in Limb-Girdle muscular dystrophy type-1C (LGMD-1C), hyperCKemia or rippling muscle disease (RMD). Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites. [provided by RefSeq, Jul 2008]

CAV3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010132194).

BP6

Variant 3-8753132-C-T is Benign according to our data. Variant chr3-8753132-C-T is described in ClinVar as [Benign]. Clinvar id is 770883.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 152 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXTR	NM_000916.4 link	c.1015G>A	p.Glu339Lys	missense_variant	Exon 4 of 4	ENST00000316793.8	NP_000907.2	P30559B2R9L7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXTR	ENST00000316793.8 link	c.1015G>A	p.Glu339Lys	missense_variant	Exon 4 of 4	1	NM_000916.4	ENSP00000324270.2		P30559
CAV3	ENST00000472766.1 link	n.155+19142C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00100

AC:

152

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00113

AC:

284

AN:

251398

Hom.:

AF XY:

0.00113

AC XY:

153

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00784

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.00144

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00132

AC:

1933

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

962

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00857

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.000543

Gnomad4 NFE exome

AF:

0.00137

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.000999

AC:

152

AN:

152174

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.00103

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00107

AC:

130

EpiCase

AF:

0.00131

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

OXTR-related disorder

Benign:1

Jun 07, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Aug 22, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0081

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.2

REVEL

Benign

0.11

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.020

Polyphen

0.47

Vest4

0.35

MVP

0.71

MPC

0.68

ClinPred

0.019

GERP RS

5.1

Varity_R

0.33

gMVP

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over