dbSNP rs201922730: ARID3A:p.Met123Leu (chr19-929895-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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. 17/24 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M123V) has been classified as Uncertain significance.

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

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023186743).

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>C	p.Met123Leu	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>C	p.Met123Leu	missense splice_region	Exon 2 of 9	ENSP00000263620.2	Q99856
ARID3A	ENST00000852898.1		c.367A>C	p.Met123Leu	missense splice_region	Exon 2 of 9	ENSP00000522957.1
ARID3A	ENST00000937801.1		c.367A>C	p.Met123Leu	missense splice_region	Exon 2 of 9	ENSP00000607860.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.20e-7

AC:

AN:

1388262

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684992

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31580

American (AMR)

AF:

0.00

AC:

AN:

35690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

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: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.5

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.060

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.34

M_CAP

Benign

0.0085

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.1

PhyloP100

-0.26

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.20

REVEL

Benign

0.064

Sift

Benign

1.0

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.064

MutPred

0.22

Gain of methylation at K124 (P = 0.0328)

MVP

0.17

MPC

0.15

ClinPred

0.051

GERP RS

-0.90

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.18

gMVP

0.025

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over