Variant X-70277755-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004312.3(ARR3):c.649A>G(p.Ile217Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,208,709 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 118 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., 10 hem., cov: 23)

Exomes 𝑓: 0.00028 ( 0 hom. 108 hem. )

Consequence

ARR3
NM_004312.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.02

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014462292).

BP6

Variant X-70277755-A-G is Benign according to our data. Variant chrX-70277755-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2660808.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARR3	NM_004312.3 linkuse as main transcript	c.649A>G	p.Ile217Val	missense_variant	10/17	ENST00000307959.9
ARR3	XM_047442105.1 linkuse as main transcript	c.673A>G	p.Ile225Val	missense_variant	9/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARR3	ENST00000307959.9 linkuse as main transcript	c.649A>G	p.Ile217Val	missense_variant	10/17	1	NM_004312.3	P1	P36575-1
ARR3	ENST00000374495.7 linkuse as main transcript	c.649A>G	p.Ile217Val	missense_variant	10/16	1			P36575-2

Frequencies

GnomAD3 genomes

AF:

0.000359

AC:

AN:

111451

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

33663

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000947

Gnomad ASJ

AF:

0.00492

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000166

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000471

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000376

AC:

AN:

180711

Hom.:

AF XY:

0.000306

AC XY:

AN XY:

65383

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00335

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000638

Gnomad NFE exome

AF:

0.000497

Gnomad OTH exome

AF:

0.000447

GnomAD4 exome

AF:

0.000283

AC:

310

AN:

1097258

Hom.:

Cov.:

AF XY:

0.000298

AC XY:

108

AN XY:

362662

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00335

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000148

Gnomad4 NFE exome

AF:

0.000242

Gnomad4 OTH exome

AF:

0.000651

GnomAD4 genome

AF:

0.000359

AC:

AN:

111451

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

33663

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000947

Gnomad4 ASJ

AF:

0.00492

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000166

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.000280

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000437

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

ARR3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.91

CADD

Benign

DANN

Benign

0.72

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.;L

MutationTaster

Benign

0.99

N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.18

N;.;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;.;T

Sift4G

Benign

0.98

T;T;T

Polyphen

0.69

P;.;D

Vest4

0.21

MVP

0.51

MPC

0.12

ClinPred

0.062

GERP RS

0.44

Varity_R

0.047

gMVP

0.17

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