rs797045264

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM5

The NM_006015.6(ARID1A):​c.5138T>A​(p.Leu1713Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. L1713P) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

ARID1A
NM_006015.6 missense

Scores

10
6
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.53
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr1-26779036-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 210260.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARID1ANM_006015.6 linkuse as main transcriptc.5138T>A p.Leu1713Gln missense_variant 20/20 ENST00000324856.13
ARID1ANM_139135.4 linkuse as main transcriptc.4487T>A p.Leu1496Gln missense_variant 20/20

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARID1AENST00000324856.13 linkuse as main transcriptc.5138T>A p.Leu1713Gln missense_variant 20/201 NM_006015.6 O14497-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.80
.;D;.;.;T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D
M_CAP
Benign
0.055
D
MetaRNN
Uncertain
0.72
D;D;D;D;D
MetaSVM
Benign
-0.90
T
MutationAssessor
Uncertain
2.8
.;M;.;.;.
MutationTaster
Benign
1.0
D;D;D;N
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-5.5
.;D;D;D;.
REVEL
Uncertain
0.45
Sift
Pathogenic
0.0
.;D;D;D;.
Sift4G
Pathogenic
0.0
.;D;D;D;.
Polyphen
0.96, 1.0, 1.0
.;D;D;D;.
Vest4
0.91, 0.94, 0.88
MutPred
0.37
.;Gain of catalytic residue at L1713 (P = 0.013);.;.;.;
MVP
0.84
MPC
1.5
ClinPred
1.0
D
GERP RS
4.8
Varity_R
0.93
gMVP
0.95

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: chr1-27105527; COSMIC: COSV61380164; COSMIC: COSV61380164; API