Variant 19-932639-G-A 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_005224.3(ARID3A):c.590G>A(p.Arg197Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000281 in 1,537,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R197W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

ARID3A
NM_005224.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

Variant links:

Genes affected

ARID3A (HGNC:3031): (AT-rich interaction domain 3A) This gene encodes a member of the ARID (AT-rich interaction domain) family of DNA binding proteins. It was found by homology to the Drosophila dead ringer gene, which is important for normal embryogenesis. Other ARID family members have roles in embryonic patterning, cell lineage gene regulation, cell cycle control, transcriptional regulation, and possibly in chromatin structure modification. [provided by RefSeq, Jul 2008]

ARID3A 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=0.17304099).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID3A	NM_005224.3 linkuse as main transcript	c.590G>A	p.Arg197Gln	missense_variant	3/9	ENST00000263620.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ARID3A	ENST00000263620.8 linkuse as main transcript	c.590G>A	p.Arg197Gln	missense_variant	3/9	1	NM_005224.3	P1
ARID3A	ENST00000587532.5 linkuse as main transcript	c.131G>A	p.Arg44Gln	missense_variant	1/6	5
ARID3A	ENST00000457152.3 linkuse as main transcript	c.77G>A	p.Arg26Gln	missense_variant, NMD_transcript_variant	1/4	5

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000338

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000114

AC:

AN:

131854

Hom.:

AF XY:

0.000152

AC XY:

AN XY:

72170

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000312

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000288

AC:

399

AN:

1385058

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

207

AN XY:

683006

show subpopulations

Gnomad4 AFR exome

AF:

0.000131

Gnomad4 AMR exome

AF:

0.0000302

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000382

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000357

Gnomad4 OTH exome

AF:

0.000122

GnomAD4 genome

AF:

0.000217

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000293

Hom.:

Bravo

AF:

0.000234

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000321

AC:

ExAC

AF:

0.0000967

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 23, 2023

The c.590G>A (p.R197Q) alteration is located in exon 3 (coding exon 2) of the ARID3A gene. This alteration results from a G to A substitution at nucleotide position 590, causing the arginine (R) at amino acid position 197 to be replaced by a glutamine (Q). 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

0.086

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.79

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

0.52

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.57

N;.

REVEL

Benign

0.13

Sift

Uncertain

0.013

D;.

Sift4G

Benign

0.33

T;T

Polyphen

1.0

D;.

Vest4

0.24

MVP

0.80

MPC

0.71

ClinPred

0.32

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.21

gMVP

0.41

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