Variant X-70277497-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_004312.3(ARR3):c.577C>T(p.Pro193Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,209,790 control chromosomes in the GnomAD database, including 1 homozygotes. There are 80 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., 13 hem., cov: 23)

Exomes 𝑓: 0.00018 ( 1 hom. 67 hem. )

Consequence

ARR3
NM_004312.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.834

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.092790484).

BP6

Variant X-70277497-C-T is Benign according to our data. Variant chrX-70277497-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660807.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-70277497-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARR3	NM_004312.3 linkuse as main transcript	c.577C>T	p.Pro193Ser	missense_variant	9/17	ENST00000307959.9
ARR3	XM_047442105.1 linkuse as main transcript	c.601C>T	p.Pro201Ser	missense_variant	8/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARR3	ENST00000307959.9 linkuse as main transcript	c.577C>T	p.Pro193Ser	missense_variant	9/17	1	NM_004312.3	P1	P36575-1
ARR3	ENST00000374495.7 linkuse as main transcript	c.577C>T	p.Pro193Ser	missense_variant	9/16	1			P36575-2

Frequencies

GnomAD3 genomes

AF:

0.000312

AC:

AN:

112172

Hom.:

Cov.:

AF XY:

0.000379

AC XY:

AN XY:

34322

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00206

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000226

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000266

AC:

AN:

180630

Hom.:

AF XY:

0.000322

AC XY:

AN XY:

65256

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000660

Gnomad ASJ exome

AF:

0.000135

Gnomad EAS exome

AF:

0.0000726

Gnomad SAS exome

AF:

0.000215

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000261

Gnomad OTH exome

AF:

0.000673

GnomAD4 exome

AF:

0.000177

AC:

194

AN:

1097618

Hom.:

Cov.:

AF XY:

0.000185

AC XY:

AN XY:

362992

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.000540

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.000296

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000151

Gnomad4 OTH exome

AF:

0.000369

GnomAD4 genome

AF:

0.000312

AC:

AN:

112172

Hom.:

Cov.:

AF XY:

0.000379

AC XY:

AN XY:

34322

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00206

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000226

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000400

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000198

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

Mar 01, 2023

ARR3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Uncertain

1.0

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.46

T;T;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.093

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

L;.;L

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-6.7

D;.;D

REVEL

Benign

0.23

Sift

Benign

0.26

T;.;T

Sift4G

Benign

0.25

T;T;T

Polyphen

1.0

D;.;D

Vest4

0.063

MVP

0.71

MPC

0.43

ClinPred

0.17

GERP RS

4.7

Varity_R

0.75

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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