Genetic Variant NM_006015.6:c.318C>G (chr1-26696721-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006015.6(ARID1A):c.318C>G(p.Asn106Lys) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N106S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

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: 0.0430

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: Illumina, G2P, Labcorp Genetics (formerly Invitae)

ARID1A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1416125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6 link	c.318C>G	p.Asn106Lys	missense_variant	Exon 1 of 20	ENST00000324856.13	NP_006006.3	O14497-1
ARID1A	NM_139135.4 link	c.318C>G	p.Asn106Lys	missense_variant	Exon 1 of 20		NP_624361.1	O14497-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13 link	c.318C>G	p.Asn106Lys	missense_variant	Exon 1 of 20	1	NM_006015.6	ENSP00000320485.7		O14497-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1219998

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

597530

African (AFR)

AF:

0.00

AC:

AN:

24022

American (AMR)

AF:

0.00

AC:

AN:

12312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18178

East Asian (EAS)

AF:

0.00

AC:

AN:

27408

South Asian (SAS)

AF:

0.00

AC:

AN:

53744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3592

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

994894

Other (OTH)

AF:

0.00

AC:

AN:

49296

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.63

T;T

M_CAP

Pathogenic

0.64

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.97

L;L

PhyloP100

0.043

PrimateAI

Pathogenic

0.98

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.099

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.86

T;T

Polyphen

0.015

B;B

Vest4

0.22

MutPred

0.18

Gain of ubiquitination at N106 (P = 0.0054);Gain of ubiquitination at N106 (P = 0.0054);

MVP

0.40

MPC

0.60

ClinPred

0.23

GERP RS

2.8

PromoterAI

0.21

Neutral

(source)

Varity_R

0.51

gMVP

0.39

Mutation Taster

=52/48

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over