NM_005224.3:c.235G>A

Variant names:

• chr19-929763-G-A
• rs116393241
• NM_005224.3:c.235G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005224.3(ARID3A):​c.235G>A​(p.Gly79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,552,824 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G79C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0081 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00088 (19 hom.)
• Consequence: ARID3A NM_005224.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0750
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020967126).
• BP6: Variant 19-929763-G-A is Benign according to our data. Variant chr19-929763-G-A is described in ClinVar as Benign. ClinVar VariationId is 783810.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00808 (1230/152212) while in subpopulation AFR AF = 0.0281 (1167/41530). AF 95% confidence interval is 0.0268. There are 17 homozygotes in GnomAd4. There are 558 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 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.235G>A	p.Gly79Ser	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.235G>A	p.Gly79Ser	missense	Exon 2 of 9	ENSP00000263620.2	Q99856
	ARID3A	ENST00000852898.1		c.235G>A	p.Gly79Ser	missense	Exon 2 of 9	ENSP00000522957.1
	ARID3A	ENST00000937801.1		c.235G>A	p.Gly79Ser	missense	Exon 2 of 9	ENSP00000607860.1

Frequencies

GnomAD3 genomes AF: 0.00808 AC: 1229 AN: 152094 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

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: 0.000162

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00178 AC: 271 AN: 152562 AF XY: 0.00152

Gnomad AFR exome AF: 0.0288

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000144

Gnomad OTH exome AF: 0.000459

GnomAD4 exome AF: 0.000877 AC: 1228 AN: 1400612 Hom.: 19 Cov.: 34 AF XY: 0.000762 AC XY: 528 AN XY: 692512

African (AFR) AF: 0.0282 AC: 916 AN: 32430

American (AMR) AF: 0.00150 AC: 55 AN: 36748

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25238

East Asian (EAS) AF: 0.0000539 AC: 2 AN: 37124

South Asian (SAS) AF: 0.0000499 AC: 4 AN: 80216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38220

Middle Eastern (MID) AF: 0.000949 AC: 5 AN: 5268

European-Non Finnish (NFE) AF: 0.000132 AC: 143 AN: 1087000

Other (OTH) AF: 0.00176 AC: 103 AN: 58368

GnomAD4 genome AF: 0.00808 AC: 1230 AN: 152212 Hom.: 17 Cov.: 32 AF XY: 0.00750 AC XY: 558 AN XY: 74420

African (AFR) AF: 0.0281 AC: 1167 AN: 41530

American (AMR) AF: 0.00196 AC: 30 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67988

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00171 Hom.: 0

Bravo AF: 0.00960

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0203 AC: 77

ESP6500EA AF: 0.000510 AC: 4

ExAC AF: 0.00196 AC: 218

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.76
DANN	Benign	0.94
DEOGEN2	Benign	0.092	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.075
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.11
Sift	Benign	0.21	T
Sift4G	Benign	0.40	T
Polyphen		0.059	B
Vest4		0.043
MVP		0.17
MPC		0.16
ClinPred		0.0073	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.12
gMVP		0.071
Mutation Taster		=98/2	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: rs116393241; hg19: chr19-929763;