Variant X-70276720-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_004312.3(ARR3):c.457G>A(p.Glu153Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000729 in 1,097,370 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000073 ( 0 hom. 3 hem. )

Consequence

ARR3
NM_004312.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38118356).

BS2

High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARR3	NM_004312.3 link	c.457G>A	p.Glu153Lys	missense_variant	Exon 8 of 17	ENST00000307959.9	NP_004303.2	P36575-1
ARR3	XM_047442105.1 link	c.481G>A	p.Glu161Lys	missense_variant	Exon 7 of 16		XP_047298061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARR3	ENST00000307959.9 link	c.457G>A	p.Glu153Lys	missense_variant	Exon 8 of 17	1	NM_004312.3	ENSP00000311538.8	P36575-1
ARR3	ENST00000374495.7 link	c.457G>A	p.Glu153Lys	missense_variant	Exon 8 of 16	1		ENSP00000363619.3	P36575-2
ARR3	ENST00000480877.6 link	c.*13G>A		downstream_gene_variant		5		ENSP00000425505.1	D6RCT3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000729

AC:

AN:

1097370

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

362728

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000832

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000692

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.457G>A (p.E153K) alteration is located in exon 8 (coding exon 7) of the ARR3 gene. This alteration results from a G to A substitution at nucleotide position 457, causing the glutamic acid (E) at amino acid position 153 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

.;.;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Pathogenic

3.1

M;.;M

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.4

D;.;D

REVEL

Benign

0.28

Sift

Benign

0.046

D;.;D

Sift4G

Benign

0.11

T;T;T

Polyphen

1.0

D;.;D

Vest4

0.41

MutPred

0.52

Gain of ubiquitination at E153 (P = 0.0146);Gain of ubiquitination at E153 (P = 0.0146);Gain of ubiquitination at E153 (P = 0.0146);

MVP

0.27

MPC

0.18

ClinPred

0.98

GERP RS

4.1

Varity_R

0.60

gMVP

0.78

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