chr1-26696458-C-G

Position:

• chr1-26696458-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006015.6(ARID1A):​c.55C>G​(p.Pro19Ala) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID1A NM_006015.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88

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 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=0.18644789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.55C>G	p.Pro19Ala	missense_variant	1/20	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.55C>G	p.Pro19Ala	missense_variant	1/20		NP_624361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.55C>G	p.Pro19Ala	missense_variant	1/20	1	NM_006015.6	ENSP00000320485
ARID1A	ENST00000457599.6	c.55C>G	p.Pro19Ala	missense_variant	1/20	5		ENSP00000387636
ARID1A	ENST00000430799.7	c.-13+2841C>G		intron_variant		5		ENSP00000390317	A2
ARID1A	ENST00000637465.1	c.-13+358C>G		intron_variant		5		ENSP00000490650

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Benign	0.84
DEOGEN2	Benign	0.073	T;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.35	T;T
M_CAP	Pathogenic	0.93	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	0.98	N;N
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	0.40	N;N
REVEL	Benign	0.053
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	1.0	T;T
Polyphen		0.022	B;B
Vest4		0.27
MutPred		0.23		Loss of glycosylation at P19 (P = 7e-04);Loss of glycosylation at P19 (P = 7e-04);
MVP		0.25
MPC		0.50
ClinPred		0.27	T
GERP RS		-0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.14
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs2080253926; hg19: chr1-27022949;