Variant chrX-70269680-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_004312.3(ARR3):c.27C>T(p.Ser9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 1,203,359 control chromosomes in the GnomAD database, including 4,057 homozygotes. There are 32,462 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.093 ( 497 hom., 2973 hem., cov: 22)

Exomes 𝑓: 0.078 ( 3560 hom. 29489 hem. )

Consequence

ARR3
NM_004312.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.19

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant X-70269680-C-T is Benign according to our data. Variant chrX-70269680-C-T is described in ClinVar as [Benign]. Clinvar id is 3056529.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-70269680-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARR3	NM_004312.3 linkuse as main transcript	c.27C>T	p.Ser9=	synonymous_variant	3/17	ENST00000307959.9
ARR3	XM_047442105.1 linkuse as main transcript	c.27C>T	p.Ser9=	synonymous_variant	2/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARR3	ENST00000307959.9 linkuse as main transcript	c.27C>T	p.Ser9=	synonymous_variant	3/17	1	NM_004312.3	P1	P36575-1
ARR3	ENST00000374495.7 linkuse as main transcript	c.27C>T	p.Ser9=	synonymous_variant	3/16	1			P36575-2
ARR3	ENST00000480877.6 linkuse as main transcript	c.-175C>T		5_prime_UTR_variant	3/8	5
ARR3	ENST00000477379.5 linkuse as main transcript	n.96C>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.0933

AC:

10352

AN:

110988

Hom.:

498

Cov.:

AF XY:

0.0894

AC XY:

2969

AN XY:

33212

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.0950

Gnomad ASJ

AF:

0.0963

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.0457

Gnomad MID

AF:

0.0970

Gnomad NFE

AF:

0.0576

Gnomad OTH

AF:

0.0918

GnomAD3 exomes

AF:

0.113

AC:

19284

AN:

171260

Hom.:

1351

AF XY:

0.109

AC XY:

6247

AN XY:

57558

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.0958

Gnomad EAS exome

AF:

0.401

Gnomad SAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.0493

Gnomad NFE exome

AF:

0.0570

Gnomad OTH exome

AF:

0.0906

GnomAD4 exome

AF:

0.0782

AC:

85382

AN:

1092317

Hom.:

3560

Cov.:

AF XY:

0.0822

AC XY:

29489

AN XY:

358881

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.350

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.0511

Gnomad4 NFE exome

AF:

0.0571

Gnomad4 OTH exome

AF:

0.100

GnomAD4 genome

AF:

0.0933

AC:

10356

AN:

111042

Hom.:

497

Cov.:

AF XY:

0.0893

AC XY:

2973

AN XY:

33276

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.0946

Gnomad4 ASJ

AF:

0.0963

Gnomad4 EAS

AF:

0.389

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.0457

Gnomad4 NFE

AF:

0.0576

Gnomad4 OTH

AF:

0.0939

Alfa

AF:

0.0709

Hom.:

1472

Bravo

AF:

0.103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ARR3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 2019

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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