chr19-971949-G-A

Variant names:

• chr19-971949-G-A
• rs1051505
• NM_005224.3:c.1666G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005224.3(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. 14/21 in silico tools predict 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 (47743 hom., cov: 29)
  • Exomes 𝑓: 0.84 (505432 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID3A NM_005224.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 27 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 -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.

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.1666G>A	p.Gly556Ser	missense	Exon 9 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.1666G>A	p.Gly556Ser	missense	Exon 9 of 9	ENSP00000263620.2	Q99856
	ARID3A	ENST00000852898.1		c.1666G>A	p.Gly556Ser	missense	Exon 9 of 9	ENSP00000522957.1
	ARID3A	ENST00000937801.1		c.1666G>A	p.Gly556Ser	missense	Exon 9 of 9	ENSP00000607860.1

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

GnomAD2 exomes AF: 0.777 AC: 166091 AN: 213706 AF XY: 0.793

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 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

African (AFR) AF: 0.711 AC: 21839 AN: 30708

American (AMR) AF: 0.581 AC: 22344 AN: 38466

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 22076 AN: 24884

East Asian (EAS) AF: 0.590 AC: 22025 AN: 37316

South Asian (SAS) AF: 0.816 AC: 67619 AN: 82904

European-Finnish (FIN) AF: 0.776 AC: 40339 AN: 52016

Middle Eastern (MID) AF: 0.888 AC: 4881 AN: 5498

European-Non Finnish (NFE) AF: 0.863 AC: 947238 AN: 1097620

Other (OTH) AF: 0.829 AC: 48688 AN: 58696

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

African (AFR) AF: 0.713 AC: 29473 AN: 41316

American (AMR) AF: 0.686 AC: 10439 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3083 AN: 3462

East Asian (EAS) AF: 0.597 AC: 3049 AN: 5108

South Asian (SAS) AF: 0.817 AC: 3925 AN: 4806

European-Finnish (FIN) AF: 0.772 AC: 8070 AN: 10458

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58465 AN: 67826

Other (OTH) AF: 0.829 AC: 1743 AN: 2102

Alfa AF: 0.880 Hom.: 24129

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 v4.9

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
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	N
PhyloP100		-0.17
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.020
Sift	Benign	0.37	T
Sift4G	Benign	0.85	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
Mutation Taster		=96/4	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

Other links and lift over

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