19-929641-G-C

Variant names:

• chr19-929641-G-C
• rs757309861
• NM_005224.3:c.113G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005224.3(ARID3A):​c.113G>C​(p.Arg38Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000131 in 1,530,106 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ARID3A NM_005224.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• Publications: 4 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2294147).

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.113G>C	p.Arg38Pro	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.113G>C	p.Arg38Pro	missense	Exon 2 of 9	ENSP00000263620.2	Q99856
	ARID3A	ENST00000852898.1		c.113G>C	p.Arg38Pro	missense	Exon 2 of 9	ENSP00000522957.1
	ARID3A	ENST00000937801.1		c.113G>C	p.Arg38Pro	missense	Exon 2 of 9	ENSP00000607860.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151996 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000781 AC: 1 AN: 128100 AF XY: 0.0000142

Gnomad AFR exome AF: 0.00

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: 0.0000206

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1378110 Hom.: 0 Cov.: 70 AF XY: 0.00000147 AC XY: 1 AN XY: 680188

African (AFR) AF: 0.00 AC: 0 AN: 30872

American (AMR) AF: 0.00 AC: 0 AN: 35470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24848

East Asian (EAS) AF: 0.00 AC: 0 AN: 35276

South Asian (SAS) AF: 0.00 AC: 0 AN: 78996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4226

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077260

Other (OTH) AF: 0.00 AC: 0 AN: 57468

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151996 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74262

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67906

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.64
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.063
Sift	Benign	0.030	D
Sift4G	Benign	0.28	T
Polyphen		0.83	P
Vest4		0.34
MutPred		0.22		Loss of methylation at R38 (P = 0.01)
MVP		0.40
MPC		0.23
ClinPred		0.11	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.30
Mutation Taster		=77/23	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: rs757309861; hg19: chr19-929641;