rs1429977258

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_006015.6(ARID1A):c.193C>G(p.Pro65Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000324 in 1,232,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P65L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

ARID1A
NM_006015.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 1.14

Publications

4 publications found

Variant links:

Genes affected

ARID1A (HGNC:11110): (AT-rich interaction domain 1A) This gene encodes a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SNF/SWI complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. It is thought that the protein encoded by this gene confers specificity to the SNF/SWI complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ARID1A Gene-Disease associations (from GenCC):

Coffin-Siris syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
intellectual disability, autosomal dominant 14
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae)

ARID1A links:

LOC124900417 (HGNC:):

LOC124900417 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15775216).

BP6

Variant 1-26696596-C-G is Benign according to our data. Variant chr1-26696596-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 445779.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ARID1A	NM_006015.6 link	c.193C>G	p.Pro65Ala	missense_variant	Exon 1 of 20	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4 link	c.193C>G	p.Pro65Ala	missense_variant	Exon 1 of 20		NP_624361.1
LOC124900417	XM_047439473.1 link	c.-191G>C		upstream_gene_variant			XP_047295429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13 link	c.193C>G	p.Pro65Ala	missense_variant	Exon 1 of 20	1	NM_006015.6	ENSP00000320485.7

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000185

AC:

AN:

1082162

Hom.:

Cov.:

AF XY:

0.00000390

AC XY:

AN XY:

512888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22612

American (AMR)

AF:

0.00

AC:

AN:

8146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14056

East Asian (EAS)

AF:

0.00

AC:

AN:

25986

South Asian (SAS)

AF:

0.00

AC:

AN:

21020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21756

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2894

European-Non Finnish (NFE)

AF:

0.00000217

AC:

AN:

922336

Other (OTH)

AF:

0.00

AC:

AN:

43356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150758

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73612

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41076

American (AMR)

AF:

0.00

AC:

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5044

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67570

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Sep 15, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 07, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Uncertain:1

Apr 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.193C>G (p.P65A) alteration is located in exon 1 (coding exon 1) of the ARID1A gene. This alteration results from a C to G substitution at nucleotide position 193, causing the proline (P) at amino acid position 65 to be replaced by an alanine (A). 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

0.066

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.073

T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.63

T;T

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.0

N;N

PhyloP100

1.1

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

0.39

N;N

REVEL

Benign

0.043

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

1.0

T;T

Vest4

0.27

ClinPred

0.29

GERP RS

2.2

PromoterAI

-0.068

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.9

Varity_R

0.13

gMVP

0.091

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over