19-929895-A-C

Variant names:

• chr19-929895-A-C
• NM_005224.3:c.367A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005224.3(ARID3A):​c.367A>C​(p.Met123Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,388,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ARID3A NM_005224.3 missense, splice_region
• Scores: Splicing: ADA: 0.02165
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023186743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID3A	NM_005224.3	c.367A>C	p.Met123Leu	missense_variant, splice_region_variant	Exon 2 of 9	ENST00000263620.8	NP_005215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID3A	ENST00000263620.8	c.367A>C	p.Met123Leu	missense_variant, splice_region_variant	Exon 2 of 9	1	NM_005224.3	ENSP00000263620.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1388262 Hom.: 0 Cov.: 35 AF XY: 0.00000146 AC XY: 1 AN XY: 684992

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.5
DANN	Benign	0.80
DEOGEN2	Benign	0.060	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.1	N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.064
Sift	Benign	1.0	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.064
MutPred		0.22		Gain of methylation at K124 (P = 0.0328);
MVP		0.17
MPC		0.15
ClinPred		0.051	T
GERP RS		-0.90
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.18
gMVP		0.025

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.022
dbscSNV1_RF	Benign	0.40
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-929895;