rs1051505

Positions:

• chr19-971949-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000263620.8(ARID3A):​c.1666G>A​(p.Gly556Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 151,504 control chromosomes in the GnomAD database, including 47,743 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.79 (47743 hom., cov: 29)
  • Exomes 𝑓: 0.84 (505432 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID3A ENST00000263620.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1359463E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID3A	NM_005224.3	c.1666G>A	p.Gly556Ser	missense_variant	9/9	ENST00000263620.8	NP_005215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID3A	ENST00000263620.8	c.1666G>A	p.Gly556Ser	missense_variant	9/9	1	NM_005224.3	ENSP00000263620	P1
ARID3A	ENST00000587532.5	c.910G>A	p.Gly304Ser	missense_variant	6/6	5		ENSP00000464969

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119307 AN: 151386 Hom.: 47717 Cov.: 29

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.826

GnomAD3 exomes AF: 0.777 AC: 166091 AN: 213706 Hom.: 66197 AF XY: 0.793 AC XY: 94050 AN XY: 118556

Gnomad AFR exome AF: 0.692

Gnomad AMR exome AF: 0.571

Gnomad ASJ exome AF: 0.886

Gnomad EAS exome AF: 0.577

Gnomad SAS exome AF: 0.813

Gnomad FIN exome AF: 0.768

Gnomad NFE exome AF: 0.858

Gnomad OTH exome AF: 0.811

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.838 AC: 1197049 AN: 1428108 Hom.: 505432 Cov.: 51 AF XY: 0.839 AC XY: 596108 AN XY: 710486

Gnomad4 AFR exome AF: 0.711

Gnomad4 AMR exome AF: 0.581

Gnomad4 ASJ exome AF: 0.887

Gnomad4 EAS exome AF: 0.590

Gnomad4 SAS exome AF: 0.816

Gnomad4 FIN exome AF: 0.776

Gnomad4 NFE exome AF: 0.863

Gnomad4 OTH exome AF: 0.829

GnomAD4 genome AF: 0.788 AC: 119374 AN: 151504 Hom.: 47743 Cov.: 29 AF XY: 0.783 AC XY: 57941 AN XY: 74016

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.891

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.862

Gnomad4 OTH AF: 0.829

Alfa AF: 0.848 Hom.: 17611

Bravo AF: 0.780

TwinsUK AF: 0.874 AC: 3241

ALSPAC AF: 0.867 AC: 3342

ESP6500AA AF: 0.761 AC: 3346

ESP6500EA AF: 0.865 AC: 7417

ExAC AF: 0.776 AC: 93322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.2
DANN	Benign	0.69
DEOGEN2	Benign	0.042	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.38	T;T
MetaRNN	Benign	0.0000011	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	N;.
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.50	N;.
REVEL	Benign	0.020
Sift	Benign	0.37	T;.
Sift4G	Benign	0.85	T;T
Polyphen		0.0	B;.
Vest4		0.051
MPC		0.26
ClinPred		0.0060	T
GERP RS		-7.2
Varity_R		0.037
gMVP		0.27

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: rs1051505; hg19: chr19-971949; COSMIC: COSV55043452; COSMIC: COSV55043452;