Genetic Variant NM_005224.3:c.367A>G (chr19-929895-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005224.3(ARID3A):c.367A>G(p.Met123Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,540,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/26 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ARID3A
NM_005224.3 missense, splice_region

Scores

Splicing: ADA: 0.7575

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.264

Publications

3 publications found

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]

ARID3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009326786).

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.367A>G	p.Met123Val	missense splice_region	Exon 2 of 9	NP_005215.1	Q99856

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARID3A	ENST00000263620.8	TSL:1 MANE Select	c.367A>G	p.Met123Val	missense splice_region	Exon 2 of 9	ENSP00000263620.2	Q99856
ARID3A	ENST00000852898.1		c.367A>G	p.Met123Val	missense splice_region	Exon 2 of 9	ENSP00000522957.1
ARID3A	ENST00000937801.1		c.367A>G	p.Met123Val	missense splice_region	Exon 2 of 9	ENSP00000607860.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD2 exomes

AF:

0.0000139

AC:

AN:

144292

AF XY:

0.0000130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000187

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000231

AC:

AN:

1388262

Hom.:

Cov.:

AF XY:

0.0000219

AC XY:

AN XY:

684992

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31580

American (AMR)

AF:

0.00

AC:

AN:

35690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.000840

AC:

AN:

35718

South Asian (SAS)

AF:

0.00

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078800

Other (OTH)

AF:

0.00

AC:

AN:

57930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000533

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.000269

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000535

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.1

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.077

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.45

M_CAP

Benign

0.013

MetaRNN

Benign

0.0093

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

PhyloP100

-0.26

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.61

REVEL

Benign

0.064

Sift

Benign

0.33

Sift4G

Benign

0.39

Polyphen

0.0

Vest4

0.068

MVP

0.24

MPC

0.16

ClinPred

0.047

GERP RS

-0.90

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.14

gMVP

0.034

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.76

dbscSNV1_RF

Benign

0.59

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.29

Position offset: -1

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over