19-929753-A-G

Position:

• chr19-929753-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005224.3(ARID3A):​c.225A>G​(p.Pro75Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 1,555,082 control chromosomes in the GnomAD database, including 554,157 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 0.86 (56180 hom., cov: 33)
  • Exomes 𝑓: 0.84 (497977 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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-3.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID3A	NM_005224.3	c.225A>G	p.Pro75Pro	synonymous_variant	2/9	ENST00000263620.8	NP_005215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID3A	ENST00000263620.8	c.225A>G	p.Pro75Pro	synonymous_variant	2/9	1	NM_005224.3	ENSP00000263620.2

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130504 AN: 152016 Hom.: 56132 Cov.: 33

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.843

GnomAD3 exomes AF: 0.847 AC: 133950 AN: 158058 Hom.: 56983 AF XY: 0.845 AC XY: 73478 AN XY: 86960

Gnomad AFR exome AF: 0.896

Gnomad AMR exome AF: 0.813

Gnomad ASJ exome AF: 0.825

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.829

Gnomad FIN exome AF: 0.836

Gnomad NFE exome AF: 0.838

Gnomad OTH exome AF: 0.833

GnomAD4 exome AF: 0.842 AC: 1181154 AN: 1402948 Hom.: 497977 Cov.: 85 AF XY: 0.841 AC XY: 583668 AN XY: 693934

Gnomad4 AFR exome AF: 0.901

Gnomad4 AMR exome AF: 0.819

Gnomad4 ASJ exome AF: 0.826

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.831

Gnomad4 FIN exome AF: 0.846

Gnomad4 NFE exome AF: 0.836

Gnomad4 OTH exome AF: 0.852

GnomAD4 genome AF: 0.859 AC: 130609 AN: 152134 Hom.: 56180 Cov.: 33 AF XY: 0.858 AC XY: 63855 AN XY: 74388

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.845

Alfa AF: 0.844 Hom.: 9923

Bravo AF: 0.859

Asia WGS AF: 0.919 AC: 3191 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.036
DANN	Benign	0.29

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: rs1799595; hg19: chr19-929753; COSMIC: COSV55043145; COSMIC: COSV55043145;