19-929811-C-T

Variant names:

• chr19-929811-C-T
• rs755008780
• NM_005224.3:c.283C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005224.3(ARID3A):​c.283C>T​(p.Arg95Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000194 in 1,545,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R95Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ARID3A NM_005224.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.454
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.014049023).

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.283C>T	p.Arg95Trp	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.283C>T	p.Arg95Trp	missense	Exon 2 of 9	ENSP00000263620.2	Q99856
	ARID3A	ENST00000852898.1		c.283C>T	p.Arg95Trp	missense	Exon 2 of 9	ENSP00000522957.1
	ARID3A	ENST00000937801.1		c.283C>T	p.Arg95Trp	missense	Exon 2 of 9	ENSP00000607860.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000206 AC: 3 AN: 145526 AF XY: 0.0000256

Gnomad AFR exome AF: 0.000132

Gnomad AMR exome AF: 0.0000813

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000172 AC: 24 AN: 1393752 Hom.: 0 Cov.: 35 AF XY: 0.0000174 AC XY: 12 AN XY: 687944

African (AFR) AF: 0.00 AC: 0 AN: 31794

American (AMR) AF: 0.0000558 AC: 2 AN: 35812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25188

East Asian (EAS) AF: 0.00 AC: 0 AN: 36120

South Asian (SAS) AF: 0.00 AC: 0 AN: 79380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41354

Middle Eastern (MID) AF: 0.000356 AC: 2 AN: 5618

European-Non Finnish (NFE) AF: 0.0000185 AC: 20 AN: 1080462

Other (OTH) AF: 0.00 AC: 0 AN: 58024

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152082 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74294

African (AFR) AF: 0.0000724 AC: 3 AN: 41420

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000587 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.00000968 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.45
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.030	D
Polyphen		0.96	D
Vest4		0.094
MVP		0.47
MPC		0.16
ClinPred		0.48	T
GERP RS		-0.084
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.049
Mutation Taster		=99/1	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: rs755008780; hg19: chr19-929811; COSMIC: COSV55043272; COSMIC: COSV55043272;