Variant 19-929637-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005224.3(ARID3A):c.109G>A(p.Gly37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 1,528,940 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 6 hom. )

Consequence

ARID3A
NM_005224.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.174

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016341805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID3A	NM_005224.3 linkuse as main transcript	c.109G>A	p.Gly37Ser	missense_variant	2/9	ENST00000263620.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID3A	ENST00000263620.8 linkuse as main transcript	c.109G>A	p.Gly37Ser	missense_variant	2/9	1	NM_005224.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000951

AC:

AN:

126172

Hom.:

AF XY:

0.0000720

AC XY:

AN XY:

69456

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000826

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000500

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.0000423

Gnomad OTH exome

AF:

0.000256

GnomAD4 exome

AF:

0.000352

AC:

484

AN:

1376860

Hom.:

Cov.:

AF XY:

0.000331

AC XY:

225

AN XY:

679424

show subpopulations

Gnomad4 AFR exome

AF:

0.0000650

Gnomad4 AMR exome

AF:

0.000141

Gnomad4 ASJ exome

AF:

0.0000402

Gnomad4 EAS exome

AF:

0.0121

Gnomad4 SAS exome

AF:

0.0000507

Gnomad4 FIN exome

AF:

0.000238

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.000139

GnomAD4 genome

AF:

0.000171

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00348

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000189

ExAC

AF:

0.0000664

AC:

Asia WGS

AF:

0.000579

AC:

AN:

3466

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

Jan 26, 2022

The c.109G>A (p.G37S) alteration is located in exon 2 (coding exon 1) of the ARID3A gene. This alteration results from a G to A substitution at nucleotide position 109, causing the glycine (G) at amino acid position 37 to be replaced by a serine (S). 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

0.082

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.72

Cadd

Benign

7.2

Dann

Benign

0.65

DEOGEN2

Benign

0.039

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.29

M_CAP

Benign

0.016

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.23

REVEL

Benign

0.033

Sift

Benign

0.52

Sift4G

Benign

0.72

Polyphen

0.0030

Vest4

0.052

MutPred

0.17

Gain of phosphorylation at G37 (P = 6e-04);

MVP

0.22

MPC

0.16

ClinPred

0.0092

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.041

gMVP

0.15

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