19-929763-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005224.3(ARID3A):c.235G>A(p.Gly79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,552,824 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G79C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0081 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00088 (19 hom.)
• Consequence: ARID3A NM_005224.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0750

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020967126).
• BP6: Variant 19-929763-G-A is Benign according to our data. Variant chr19-929763-G-A is described in ClinVar as [Benign]. Clinvar id is 783810.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00808 (1230/152212) while in subpopulation AFR AF= 0.0281 (1167/41530). AF 95% confidence interval is 0.0268. There are 17 homozygotes in gnomad4. There are 558 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID3A	NM_005224.3	c.235G>A	p.Gly79Ser	missense_variant	2/9	ENST00000263620.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID3A	ENST00000263620.8	c.235G>A	p.Gly79Ser	missense_variant	2/9	1	NM_005224.3	P1

Frequencies

GnomAD3 genomes AF: 0.00808 AC: 1229 AN: 152094 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

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: 0.000162

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00178 AC: 271 AN: 152562 Hom.: 6 AF XY: 0.00152 AC XY: 127 AN XY: 83554

Gnomad AFR exome AF: 0.0288

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000424

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000144

Gnomad OTH exome AF: 0.000459

GnomAD4 exome AF: 0.000877 AC: 1228 AN: 1400612 Hom.: 19 Cov.: 34 AF XY: 0.000762 AC XY: 528 AN XY: 692512

Gnomad4 AFR exome AF: 0.0282

Gnomad4 AMR exome AF: 0.00150

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000539

Gnomad4 SAS exome AF: 0.0000499

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000132

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.00808 AC: 1230 AN: 152212 Hom.: 17 Cov.: 32 AF XY: 0.00750 AC XY: 558 AN XY: 74420

Gnomad4 AFR AF: 0.0281

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.000264 Hom.: 0

Bravo AF: 0.00960

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0203 AC: 77

ESP6500EA AF: 0.000510 AC: 4

ExAC AF: 0.00196 AC: 218

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	0.76
Dann	Benign	0.94
DEOGEN2	Benign	0.092	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.11
Sift	Benign	0.21	T
Sift4G	Benign	0.40	T
Polyphen		0.059	B
Vest4		0.043
MVP		0.17
MPC		0.16
ClinPred		0.0073	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.12
gMVP		0.071

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: rs116393241; hg19: chr19-929763;