rs140505250

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P351L) has been classified as Likely benign.

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

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

myopia 26, X-linked, female-limited
Inheritance: XL Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ARR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ARR3	NM_004312.3 link	c.1052C>G	p.Pro351Arg	missense_variant	Exon 15 of 17	ENST00000307959.9	NP_004303.2	P36575-1
ARR3	XM_047442105.1 link	c.1076C>G	p.Pro359Arg	missense_variant	Exon 14 of 16		XP_047298061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARR3	ENST00000307959.9 link	c.1052C>G	p.Pro351Arg	missense_variant	Exon 15 of 17	1	NM_004312.3	ENSP00000311538.8		P36575-1
ARR3	ENST00000374495.7 link	c.1052C>G	p.Pro351Arg	missense_variant	Exon 15 of 16	1		ENSP00000363619.3		P36575-2

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

193

AN:

110960

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00158

AC:

290

AN:

183385

AF XY:

0.00144

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 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

African (AFR)

AF:

0.0000758

AC:

AN:

26395

American (AMR)

AF:

0.000739

AC:

AN:

35202

Ashkenazi Jewish (ASJ)

AF:

0.00150

AC:

AN:

19384

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.000757

AC:

AN:

54141

European-Finnish (FIN)

AF:

0.00205

AC:

AN:

40527

Middle Eastern (MID)

AF:

0.000243

AC:

AN:

4116

European-Non Finnish (NFE)

AF:

0.00203

AC:

1707

AN:

842076

Other (OTH)

AF:

0.00139

AC:

AN:

46086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

155

233

310

388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00174

AC:

193

AN:

111014

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

AN XY:

33226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30487

American (AMR)

AF:

0.000668

AC:

AN:

10472

Ashkenazi Jewish (ASJ)

AF:

0.00114

AC:

AN:

2634

East Asian (EAS)

AF:

0.00

AC:

AN:

3511

South Asian (SAS)

AF:

0.000389

AC:

AN:

2570

European-Finnish (FIN)

AF:

0.00233

AC:

AN:

6010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00314

AC:

166

AN:

52917

Other (OTH)

AF:

0.00132

AC:

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Sep 22, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

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

PhyloP100

6.8

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

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over