Variant chrX-70276429-C-T 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.346-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000436 in 1,209,462 control chromosomes in the GnomAD database, including 2 homozygotes. There are 134 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., 64 hem., cov: 23)

Exomes 𝑓: 0.00025 ( 1 hom. 70 hem. )

Consequence

ARR3
NM_004312.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.000009303

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.256

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-70276429-C-T is Benign according to our data. Variant chrX-70276429-C-T is described in ClinVar as [Benign]. Clinvar id is 711141.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 64 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARR3	NM_004312.3 linkuse as main transcript	c.346-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000307959.9
ARR3	XM_047442105.1 linkuse as main transcript	c.370-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ARR3	ENST00000307959.9 linkuse as main transcript	c.346-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_004312.3	P1	P36575-1
ARR3	ENST00000374495.7 linkuse as main transcript	c.346-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1			P36575-2
ARR3	ENST00000480877.6 linkuse as main transcript	c.193-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

252

AN:

112089

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

AN XY:

34273

show subpopulations

Gnomad AFR

AF:

0.00796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000282

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:

0.0000188

Gnomad OTH

AF:

0.00197

GnomAD3 exomes

AF:

0.000748

AC:

137

AN:

183161

Hom.:

AF XY:

0.000577

AC XY:

AN XY:

67617

show subpopulations

Gnomad AFR exome

AF:

0.00914

Gnomad AMR exome

AF:

0.000584

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000251

AC:

275

AN:

1097321

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

AN XY:

362701

show subpopulations

Gnomad4 AFR exome

AF:

0.00827

Gnomad4 AMR exome

AF:

0.000540

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000555

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.000716

GnomAD4 genome

AF:

0.00225

AC:

252

AN:

112141

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

AN XY:

34335

show subpopulations

Gnomad4 AFR

AF:

0.00794

Gnomad4 AMR

AF:

0.000281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00195

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.00258

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.4

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000093

dbscSNV1_RF

Benign

0.038

SpliceAI score (max)

0.020

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