dbSNP rs1557569082: ARID1A:p.Glu23Lys (chr1-26696470-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006015.6(ARID1A):c.67G>A(p.Glu23Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARID1A
NM_006015.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.01

Publications

0 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: Labcorp Genetics (formerly Invitae), G2P, Illumina

ARID1A links:

LOC124900417 (HGNC:):

LOC124900417 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27919313).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006015.6. 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
	ARID1A	NM_006015.6	MANE Select	c.67G>A	p.Glu23Lys	missense	Exon 1 of 20	NP_006006.3
	ARID1A	NM_139135.4		c.67G>A	p.Glu23Lys	missense	Exon 1 of 20	NP_624361.1	O14497-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARID1A	ENST00000324856.13	TSL:1 MANE Select	c.67G>A	p.Glu23Lys	missense	Exon 1 of 20	ENSP00000320485.7	O14497-1
ARID1A	ENST00000850904.1		c.67G>A	p.Glu23Lys	missense	Exon 1 of 20	ENSP00000520984.1	A0ABJ7H312
ARID1A	ENST00000457599.7	TSL:5	c.67G>A	p.Glu23Lys	missense	Exon 1 of 20	ENSP00000387636.2	O14497-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1126786

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

545124

African (AFR)

AF:

0.00

AC:

AN:

22886

American (AMR)

AF:

0.00

AC:

AN:

10018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15160

East Asian (EAS)

AF:

0.00

AC:

AN:

25868

South Asian (SAS)

AF:

0.00

AC:

AN:

34272

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3002

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

947666

Other (OTH)

AF:

0.00

AC:

AN:

44658

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

0.0041

Eigen_PC

Benign

0.024

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.97

PhyloP100

3.0

PrimateAI

Pathogenic

0.98

PROVEAN

Benign

-0.93

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Benign

0.28

Polyphen

0.94

Vest4

0.18

MutPred

0.12

Gain of methylation at E23 (P = 0.0146)

MVP

0.29

MPC

0.58

ClinPred

0.50

GERP RS

2.9

PromoterAI

-0.11

Neutral

(source)

Varity_R

0.59

gMVP

0.57

Mutation Taster

=81/19

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

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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