19-929673-C-T

Variant names:

• chr19-929673-C-T
• NM_005224.3:c.145C>T

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.145C>T​(p.Pro49Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID3A NM_005224.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76
• 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: 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=0.17704359).

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.145C>T	p.Pro49Ser	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.145C>T	p.Pro49Ser	missense	Exon 2 of 9	ENSP00000263620.2	Q99856
	ARID3A	ENST00000852898.1		c.145C>T	p.Pro49Ser	missense	Exon 2 of 9	ENSP00000522957.1
	ARID3A	ENST00000937801.1		c.145C>T	p.Pro49Ser	missense	Exon 2 of 9	ENSP00000607860.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1401960 Hom.: 0 Cov.: 70 AF XY: 0.00 AC XY: 0 AN XY: 693660

African (AFR) AF: 0.00 AC: 0 AN: 32636

American (AMR) AF: 0.00 AC: 0 AN: 37710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25250

East Asian (EAS) AF: 0.00 AC: 0 AN: 37416

South Asian (SAS) AF: 0.00 AC: 0 AN: 80724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4634

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090154

Other (OTH) AF: 0.00 AC: 0 AN: 58480

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	0.10
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T
Eigen	Benign	0.063
Eigen_PC	Benign	0.068
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.60	T
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.063
Sift	Benign	0.15	T
Sift4G	Benign	0.76	T
Polyphen		0.90	P
Vest4		0.17
MutPred		0.22		Gain of phosphorylation at P49 (P = 0.0024)
MVP		0.51
MPC		0.16
ClinPred		0.62	D
GERP RS		3.4
Varity_R		0.076
gMVP		0.30
Mutation Taster		=92/8	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

hg19: chr19-929673; COSMIC: COSV104557059; COSMIC: COSV104557059;