19-965043-T-C

Variant names:

• chr19-965043-T-C
• rs12608658
• NM_005224.3:c.1161T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005224.3(ARID3A):​c.1161T>C​(p.Asn387Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.969 in 1,613,254 control chromosomes in the GnomAD database, including 758,424 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.95 (68358 hom., cov: 31)
  • Exomes 𝑓: 0.97 (690066 hom.)
• Consequence: ARID3A NM_005224.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• Publications: 15 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-0.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID3A	NM_005224.3	c.1161T>C	p.Asn387Asn	synonymous_variant	Exon 6 of 9	ENST00000263620.8	NP_005215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID3A	ENST00000263620.8	c.1161T>C	p.Asn387Asn	synonymous_variant	Exon 6 of 9	1	NM_005224.3	ENSP00000263620.2
ARID3A	ENST00000587532.5	c.702T>C	p.Asn234Asn	synonymous_variant	Exon 4 of 6	5		ENSP00000464969.3
ARID3A	ENST00000585733.2	n.354T>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.947 AC: 143978 AN: 152084 Hom.: 68316 Cov.: 31

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.981

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.977

Gnomad OTH AF: 0.957

GnomAD2 exomes AF: 0.956 AC: 237444 AN: 248380 AF XY: 0.960

Gnomad AFR exome AF: 0.889

Gnomad AMR exome AF: 0.863

Gnomad ASJ exome AF: 0.980

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.995

Gnomad NFE exome AF: 0.977

Gnomad OTH exome AF: 0.963

GnomAD4 exome AF: 0.972 AC: 1419474 AN: 1461052 Hom.: 690066 Cov.: 74 AF XY: 0.972 AC XY: 706287 AN XY: 726842

African (AFR) AF: 0.888 AC: 29721 AN: 33480

American (AMR) AF: 0.869 AC: 38838 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.980 AC: 25589 AN: 26116

East Asian (EAS) AF: 1.00 AC: 39695 AN: 39700

South Asian (SAS) AF: 0.957 AC: 82487 AN: 86236

European-Finnish (FIN) AF: 0.994 AC: 52517 AN: 52810

Middle Eastern (MID) AF: 0.954 AC: 5501 AN: 5764

European-Non Finnish (NFE) AF: 0.977 AC: 1086594 AN: 1111862

Other (OTH) AF: 0.969 AC: 58532 AN: 60374

GnomAD4 genome AF: 0.947 AC: 144075 AN: 152202 Hom.: 68358 Cov.: 31 AF XY: 0.947 AC XY: 70452 AN XY: 74416

African (AFR) AF: 0.890 AC: 36940 AN: 41498

American (AMR) AF: 0.900 AC: 13747 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.981 AC: 3406 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5175 AN: 5176

South Asian (SAS) AF: 0.959 AC: 4627 AN: 4826

European-Finnish (FIN) AF: 0.996 AC: 10567 AN: 10614

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.977 AC: 66439 AN: 68022

Other (OTH) AF: 0.958 AC: 2023 AN: 2112

Alfa AF: 0.969 Hom.: 30335

Bravo AF: 0.937

Asia WGS AF: 0.981 AC: 3411 AN: 3478

EpiCase AF: 0.975

EpiControl AF: 0.974

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.082
DANN	Benign	0.36
PhyloP100		-0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs12608658; hg19: chr19-965043; COSMIC: COSV108014952; COSMIC: COSV108014952;