Variant X-70269684-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004312.3(ARR3):c.31A>G(p.Asn11Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000415 in 1,203,976 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

ARR3
NM_004312.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.54

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23422167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARR3	NM_004312.3 link	c.31A>G	p.Asn11Asp	missense_variant	Exon 3 of 17	ENST00000307959.9	NP_004303.2	P36575-1
ARR3	XM_047442105.1 link	c.31A>G	p.Asn11Asp	missense_variant	Exon 2 of 16		XP_047298061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARR3	ENST00000307959.9 link	c.31A>G	p.Asn11Asp	missense_variant	Exon 3 of 17	1	NM_004312.3	ENSP00000311538.8	P36575-1
ARR3	ENST00000374495.7 link	c.31A>G	p.Asn11Asp	missense_variant	Exon 3 of 16	1		ENSP00000363619.3	P36575-2
ARR3	ENST00000480877 link	c.-171A>G		5_prime_UTR_variant	Exon 3 of 8	5		ENSP00000425505.1	D6RCT3
ARR3	ENST00000477379.5 link	n.100A>G		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

111120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33360

show subpopulations

Gnomad AFR

AF:

0.0000328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000192

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000183

AC:

AN:

1092856

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

359000

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.0000270

AC:

AN:

111120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33360

show subpopulations

Gnomad4 AFR

AF:

0.0000328

Gnomad4 AMR

AF:

0.000192

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

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

Aug 04, 2024

The c.31A>G (p.N11D) alteration is located in exon 3 (coding exon 2) of the ARR3 gene. This alteration results from a A to G substitution at nucleotide position 31, causing the asparagine (N) at amino acid position 11 to be replaced by an aspartic acid (D). 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

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

.;.;T

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;L

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.5

N;.;N

REVEL

Benign

0.054

Sift

Benign

0.23

T;.;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.091

B;.;B

Vest4

0.24

MutPred

0.46

Loss of MoRF binding (P = 0.0564);Loss of MoRF binding (P = 0.0564);Loss of MoRF binding (P = 0.0564);

MVP

0.43

MPC

0.084

ClinPred

0.79

GERP RS

4.5

Varity_R

0.40

gMVP

0.81

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