chr19-929640-C-T

Variant names:

• chr19-929640-C-T
• rs372928434
• NM_005224.3:c.112C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005224.3(ARID3A):​c.112C>T​(p.Arg38Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000771 in 1,530,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. R38Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000071 (0 hom.)
• Consequence: ARID3A NM_005224.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19905216).

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.112C>T	p.Arg38Trp	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.112C>T	p.Arg38Trp	missense	Exon 2 of 9	ENSP00000263620.2	Q99856
	ARID3A	ENST00000852898.1		c.112C>T	p.Arg38Trp	missense	Exon 2 of 9	ENSP00000522957.1
	ARID3A	ENST00000937801.1		c.112C>T	p.Arg38Trp	missense	Exon 2 of 9	ENSP00000607860.1

Frequencies

GnomAD3 genomes AF: 0.000132 AC: 20 AN: 152062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000706 AC: 9 AN: 127510 AF XY: 0.0000855

Gnomad AFR exome AF: 0.000543

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000104

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000711 AC: 98 AN: 1377954 Hom.: 0 Cov.: 69 AF XY: 0.0000721 AC XY: 49 AN XY: 680004

African (AFR) AF: 0.0000972 AC: 3 AN: 30854

American (AMR) AF: 0.0000282 AC: 1 AN: 35444

Ashkenazi Jewish (ASJ) AF: 0.0000402 AC: 1 AN: 24856

East Asian (EAS) AF: 0.00 AC: 0 AN: 35272

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 78998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4224

European-Non Finnish (NFE) AF: 0.0000743 AC: 80 AN: 1077202

Other (OTH) AF: 0.000191 AC: 11 AN: 57442

GnomAD4 genome AF: 0.000132 AC: 20 AN: 152062 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74282

African (AFR) AF: 0.000338 AC: 14 AN: 41440

American (AMR) AF: 0.000196 AC: 3 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67942

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

Alfa AF: 0.000146 Hom.: 0

Bravo AF: 0.000113

ExAC AF: 0.0000321 AC: 3

Asia WGS AF: 0.000290 AC: 1 AN: 3466

ClinVar

ClinVar submissions as Germline

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	0.19
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.60	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.5
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.067
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.026	D
Polyphen		0.99	D
Vest4		0.28
MutPred		0.28		Loss of methylation at R38 (P = 0.01)
MVP		0.68
MPC		0.16
ClinPred		0.041	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.11
gMVP		0.25
Mutation Taster		=89/11	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: rs372928434; hg19: chr19-929640;