19-929811-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005224.3(ARID3A):​c.283C>T​(p.Arg95Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000194 in 1,545,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R95Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ARID3A
NM_005224.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.454
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.014049023).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARID3ANM_005224.3 linkc.283C>T p.Arg95Trp missense_variant Exon 2 of 9 ENST00000263620.8 NP_005215.1 Q99856

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARID3AENST00000263620.8 linkc.283C>T p.Arg95Trp missense_variant Exon 2 of 9 1 NM_005224.3 ENSP00000263620.2 Q99856

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152082
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
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
GnomAD3 exomes
AF:
0.0000206
AC:
3
AN:
145526
Hom.:
0
AF XY:
0.0000256
AC XY:
2
AN XY:
78278
show subpopulations
Gnomad AFR exome
AF:
0.000132
Gnomad AMR exome
AF:
0.0000813
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000172
AC:
24
AN:
1393752
Hom.:
0
Cov.:
35
AF XY:
0.0000174
AC XY:
12
AN XY:
687944
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000558
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:
0.0000185
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
152082
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000587
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.00000968
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.283C>T (p.R95W) alteration is located in exon 2 (coding exon 1) of the ARID3A gene. This alteration results from a C to T substitution at nucleotide position 283, causing the arginine (R) at amino acid position 95 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.65
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.081
N
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.052
D
MetaRNN
Benign
0.014
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.4
L
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.0
N
REVEL
Benign
0.13
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.030
D
Polyphen
0.96
D
Vest4
0.094
MVP
0.47
MPC
0.16
ClinPred
0.48
T
GERP RS
-0.084
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.10
gMVP
0.049

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755008780; hg19: chr19-929811; COSMIC: COSV55043272; COSMIC: COSV55043272; API