dbSNP rs2080253926: ARID1A:p.Pro19Thr (chr1-26696458-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006015.6(ARID1A):c.55C>A(p.Pro19Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000878 in 1,139,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. P19A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.8e-7 ( 0 hom. )

Consequence

ARID1A
NM_006015.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.88

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 links:

LOC124900417 (HGNC:):

LOC124900417 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19815555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6 link	c.55C>A	p.Pro19Thr	missense_variant	Exon 1 of 20	ENST00000324856.13	NP_006006.3	O14497-1
ARID1A	NM_139135.4 link	c.55C>A	p.Pro19Thr	missense_variant	Exon 1 of 20		NP_624361.1	O14497-2
LOC124900417	XM_047439473.1 link	c.-53G>T		upstream_gene_variant			XP_047295429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARID1A	ENST00000324856.13 link	c.55C>A	p.Pro19Thr	missense_variant	Exon 1 of 20	1	NM_006015.6	ENSP00000320485.7	O14497-1
ARID1A	ENST00000457599.6 link	c.55C>A	p.Pro19Thr	missense_variant	Exon 1 of 20	5		ENSP00000387636.2	O14497-2
ARID1A	ENST00000430799.7 link	c.-13+2841C>A		intron_variant	Intron 1 of 19	5		ENSP00000390317.3	H0Y488
ARID1A	ENST00000637465.1 link	c.-13+358C>A		intron_variant	Intron 1 of 2	5		ENSP00000490650.1	A0A1B0GVT5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.78e-7

AC:

AN:

1139572

Hom.:

Cov.:

AF XY:

0.00000181

AC XY:

AN XY:

552996

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000105

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.099

T;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.40

T;T

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.0

N;N

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

0.13

N;N

REVEL

Benign

0.054

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.22

T;T

Polyphen

0.049

B;B

Vest4

0.29

MutPred

0.24

Gain of phosphorylation at P19 (P = 0.0042);Gain of phosphorylation at P19 (P = 0.0042);

MVP

0.26

MPC

0.58

ClinPred

0.30

GERP RS

-0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.30

gMVP

0.30

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over