19-929889-G-A

Variant names:

• chr19-929889-G-A
• rs772606131
• NM_005224.3:c.361G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005224.3(ARID3A):​c.361G>A​(p.Glu121Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000188 in 1,540,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ARID3A NM_005224.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10941851).

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.361G>A	p.Glu121Lys	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.361G>A	p.Glu121Lys	missense	Exon 2 of 9	ENSP00000263620.2	Q99856
	ARID3A	ENST00000852898.1		c.361G>A	p.Glu121Lys	missense	Exon 2 of 9	ENSP00000522957.1
	ARID3A	ENST00000937801.1		c.361G>A	p.Glu121Lys	missense	Exon 2 of 9	ENSP00000607860.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD2 exomes AF: 0.0000347 AC: 5 AN: 144250 AF XY: 0.0000389

Gnomad AFR exome AF: 0.000132

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000235

GnomAD4 exome AF: 0.0000173 AC: 24 AN: 1388556 Hom.: 0 Cov.: 34 AF XY: 0.0000204 AC XY: 14 AN XY: 685110

African (AFR) AF: 0.0000317 AC: 1 AN: 31586

American (AMR) AF: 0.00 AC: 0 AN: 35688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35724

South Asian (SAS) AF: 0.000139 AC: 11 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00000742 AC: 8 AN: 1078816

Other (OTH) AF: 0.0000690 AC: 4 AN: 57934

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74338

African (AFR) AF: 0.000121 AC: 5 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000174 AC: 1

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.13
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.59
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.076
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.088
Sift	Benign	0.030	D
Sift4G	Benign	0.59	T
Polyphen		0.34	B
Vest4		0.11
MutPred		0.22		Gain of ubiquitination at E121 (P = 0.0121)
MVP		0.37
MPC		0.23
ClinPred		0.055	T
GERP RS		3.0
Varity_R		0.27
gMVP		0.094
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs772606131; hg19: chr19-929889;