NM_006015.6:c.5965C>G

Variant names:

• chr1-26779863-C-G
• NM_006015.6:c.5965C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Moderate PP5_Moderate

The NM_006015.6(ARID1A):​c.5965C>G​(p.Arg1989Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID1A NM_006015.6 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.79

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.922
• PP5: Variant 1-26779863-C-G is Pathogenic according to our data. Variant chr1-26779863-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2920687.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.5965C>G	p.Arg1989Gly	missense_variant	Exon 20 of 20	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.5314C>G	p.Arg1772Gly	missense_variant	Exon 20 of 20		NP_624361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.5965C>G	p.Arg1989Gly	missense_variant	Exon 20 of 20	1	NM_006015.6	ENSP00000320485.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, autosomal dominant 14 Pathogenic:1

Jul 05, 2023

Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	.;D;.;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	1.0	D;D;D;D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.92	D;D;D;D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.7	.;M;.;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.9	.;D;D;D;.
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	.;D;D;D;.
Sift4G	Pathogenic	0.0	.;D;D;D;.
Polyphen		1.0, 1.0, 1.0	.;D;D;D;.
Vest4		0.92, 0.95, 0.94
MutPred		0.80		.;Loss of sheet (P = 0.0817);.;.;.;
MVP		0.92
MPC		1.7
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.95
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-27106354;