Variant rs140505250 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_004312.3(ARR3):c.1052C>G(p.Pro351Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00177 in 1,209,147 control chromosomes in the GnomAD database, including 1 homozygotes. There are 690 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., 51 hem., cov: 21)

Exomes 𝑓: 0.0018 ( 1 hom. 639 hem. )

Consequence

ARR3
NM_004312.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.82

Variant links:

Genes affected

ARR3 (HGNC:710): (arrestin 3) The protein encoded by this gene is a non-visual arrestin which binds to agonist-activated, phosphorylated G protein-coupled receptors. This binding uncouples the receptor from the heterotrimeric G protein, resulting in termination of the G protein-coupled receptor signaling. The encoded protein also is a part of the centrosome, interacting with gamma-tubulin to help regulate proper centrosome function. [provided by RefSeq, May 2016]

ARR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14858988).

BP6

Variant X-70280804-C-G is Benign according to our data. Variant chrX-70280804-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3352517.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 51 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARR3	NM_004312.3 linkuse as main transcript	c.1052C>G	p.Pro351Arg	missense_variant	15/17	ENST00000307959.9	NP_004303.2	P36575-1
ARR3	XM_047442105.1 linkuse as main transcript	c.1076C>G	p.Pro359Arg	missense_variant	14/16		XP_047298061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARR3	ENST00000307959.9 linkuse as main transcript	c.1052C>G	p.Pro351Arg	missense_variant	15/17	1	NM_004312.3	ENSP00000311538.8		P36575-1
ARR3	ENST00000374495.7 linkuse as main transcript	c.1052C>G	p.Pro351Arg	missense_variant	15/16	1		ENSP00000363619.3		P36575-2

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

193

AN:

110960

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

AN XY:

33162

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000669

Gnomad ASJ

AF:

0.00114

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000388

Gnomad FIN

AF:

0.00233

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00314

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.00158

AC:

290

AN:

183385

Hom.:

AF XY:

0.00144

AC XY:

AN XY:

67821

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000547

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000629

Gnomad FIN exome

AF:

0.00181

Gnomad NFE exome

AF:

0.00261

Gnomad OTH exome

AF:

0.00177

GnomAD4 exome

AF:

0.00178

AC:

1953

AN:

1098133

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

639

AN XY:

363519

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.000739

Gnomad4 ASJ exome

AF:

0.00150

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000757

Gnomad4 FIN exome

AF:

0.00205

Gnomad4 NFE exome

AF:

0.00203

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00174

AC:

193

AN:

111014

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

AN XY:

33226

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000668

Gnomad4 ASJ

AF:

0.00114

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000389

Gnomad4 FIN

AF:

0.00233

Gnomad4 NFE

AF:

0.00314

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.00288

Hom.:

Bravo

AF:

0.00134

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00253

AC:

ExAC

AF:

0.00175

AC:

212

EpiCase

AF:

0.00218

EpiControl

AF:

0.00243

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ARR3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 22, 2024

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

.;.;T

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Pathogenic

3.2

M;.;M

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-7.6

D;.;D

REVEL

Pathogenic

0.65

Sift

Pathogenic

0.0

D;.;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.87

MVP

0.84

MPC

0.44

ClinPred

0.14

GERP RS

4.8

Varity_R

0.94

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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