chr19-966693-C-T

Variant names:

• chr19-966693-C-T
• rs6510986
• NM_005224.3:c.1320C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005224.3(ARID3A):​c.1320C>T​(p.Ala440Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 1,610,972 control chromosomes in the GnomAD database, including 572,690 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (48519 hom., cov: 34)
  • Exomes 𝑓: 0.84 (524171 hom.)
• Consequence: ARID3A NM_005224.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.64

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-3.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID3A	NM_005224.3	c.1320C>T	p.Ala440Ala	synonymous_variant	Exon 7 of 9	ENST00000263620.8	NP_005215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID3A	ENST00000263620.8	c.1320C>T	p.Ala440Ala	synonymous_variant	Exon 7 of 9	1	NM_005224.3	ENSP00000263620.2
ARID3A	ENST00000587532.5	c.739+1613C>T		intron_variant	Intron 4 of 5	5		ENSP00000464969.3
ARID3A	ENST00000590749.2	n.-94C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120537 AN: 152022 Hom.: 48484 Cov.: 34

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.826

GnomAD2 exomes AF: 0.787 AC: 191185 AN: 242904 AF XY: 0.801

Gnomad AFR exome AF: 0.715

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.894

Gnomad EAS exome AF: 0.586

Gnomad FIN exome AF: 0.786

Gnomad NFE exome AF: 0.871

Gnomad OTH exome AF: 0.820

GnomAD4 exome AF: 0.844 AC: 1231870 AN: 1458832 Hom.: 524171 Cov.: 75 AF XY: 0.845 AC XY: 613510 AN XY: 725638

Gnomad4 AFR exome AF: 0.719 AC: 24045 AN: 33422

Gnomad4 AMR exome AF: 0.595 AC: 26420 AN: 44398

Gnomad4 ASJ exome AF: 0.892 AC: 23286 AN: 26104

Gnomad4 EAS exome AF: 0.588 AC: 23279 AN: 39612

Gnomad4 SAS exome AF: 0.824 AC: 71031 AN: 86166

Gnomad4 FIN exome AF: 0.790 AC: 41263 AN: 52224

Gnomad4 NFE exome AF: 0.871 AC: 967167 AN: 1110900

Gnomad4 Remaining exome AF: 0.834 AC: 50263 AN: 60248

GnomAD4 genome AF: 0.793 AC: 120610 AN: 152140 Hom.: 48519 Cov.: 34 AF XY: 0.788 AC XY: 58593 AN XY: 74374

Gnomad4 AFR AF: 0.714 AC: 0.714186 AN: 0.714186

Gnomad4 AMR AF: 0.688 AC: 0.687525 AN: 0.687525

Gnomad4 ASJ AF: 0.893 AC: 0.892857 AN: 0.892857

Gnomad4 EAS AF: 0.596 AC: 0.596229 AN: 0.596229

Gnomad4 SAS AF: 0.825 AC: 0.824907 AN: 0.824907

Gnomad4 FIN AF: 0.789 AC: 0.788878 AN: 0.788878

Gnomad4 NFE AF: 0.869 AC: 0.868874 AN: 0.868874

Gnomad4 OTH AF: 0.828 AC: 0.827962 AN: 0.827962

Alfa AF: 0.849 Hom.: 17892

Bravo AF: 0.781

Asia WGS AF: 0.717 AC: 2494 AN: 3478

EpiCase AF: 0.873

EpiControl AF: 0.880

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.14
DANN	Benign	0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6510986; hg19: chr19-966693; COSMIC: COSV55043102; COSMIC: COSV55043102;