chr19-929637-G-A

Variant names:

• chr19-929637-G-A
• rs3746142
• NM_005224.3:c.109G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 15/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.174
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016341805).
• BS2: High Homozygotes in GnomAdExome4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005224.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID3A	NM_005224.3	MANE Select	c.109G>A	p.Gly37Ser	missense	Exon 2 of 9	NP_005215.1	Q99856

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID3A	ENST00000263620.8	TSL:1 MANE Select	c.109G>A	p.Gly37Ser	missense	Exon 2 of 9	ENSP00000263620.2	Q99856
	ARID3A	ENST00000852898.1		c.109G>A	p.Gly37Ser	missense	Exon 2 of 9	ENSP00000522957.1
	ARID3A	ENST00000937801.1		c.109G>A	p.Gly37Ser	missense	Exon 2 of 9	ENSP00000607860.1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 151970 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.0000951 AC: 12 AN: 126172 AF XY: 0.0000720

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 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.: 6 Cov.: 70 AF XY: 0.000331 AC XY: 225 AN XY: 679424

African (AFR) AF: 0.0000650 AC: 2 AN: 30788

American (AMR) AF: 0.000141 AC: 5 AN: 35416

Ashkenazi Jewish (ASJ) AF: 0.0000402 AC: 1 AN: 24846

East Asian (EAS) AF: 0.0121 AC: 425 AN: 35134

South Asian (SAS) AF: 0.0000507 AC: 4 AN: 78938

European-Finnish (FIN) AF: 0.000238 AC: 8 AN: 33594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4206

European-Non Finnish (NFE) AF: 0.0000288 AC: 31 AN: 1076522

Other (OTH) AF: 0.000139 AC: 8 AN: 57416

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152080 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74360

African (AFR) AF: 0.0000241 AC: 1 AN: 41514

American (AMR) AF: 0.000196 AC: 3 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00348 AC: 18 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67916

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.000189

ExAC AF: 0.0000664 AC: 6

Asia WGS AF: 0.000579 AC: 2 AN: 3466

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.2
DANN	Benign	0.65
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.17
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.033
Sift	Benign	0.52	T
Sift4G	Benign	0.72	T
Polyphen		0.0030	B
Vest4		0.052
MutPred		0.17		Gain of phosphorylation at G37 (P = 6e-04)
MVP		0.22
MPC		0.16
ClinPred		0.0092	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.041
gMVP		0.15
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs3746142; hg19: chr19-929637;