Variant 2-96550692-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_212481.3(ARID5A):c.529G>A(p.Glu177Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000447 in 1,596,864 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00045 ( 2 hom. )

Consequence

ARID5A
NM_212481.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

Variant links:

Genes affected

ARID5A (HGNC:17361): (AT-rich interaction domain 5A) Members of the ARID protein family, including ARID5A, have diverse functions but all appear to play important roles in development, tissue-specific gene expression, and regulation of cell growth (Patsialou et al., 2005 [PubMed 15640446]).[supplied by OMIM, Mar 2008]

ARID5A links:

ARID5A (HGNC:):

ARID5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022940278).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID5A	NM_212481.3 linkuse as main transcript	c.529G>A	p.Glu177Lys	missense_variant	6/7	ENST00000357485.8	NP_997646.1	Q03989-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID5A	ENST00000357485.8 linkuse as main transcript	c.529G>A	p.Glu177Lys	missense_variant	6/7	1	NM_212481.3	ENSP00000350078.3		Q03989-1

Frequencies

GnomAD3 genomes

AF:

0.000369

AC:

AN:

151926

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000491

AC:

107

AN:

217704

Hom.:

AF XY:

0.000418

AC XY:

AN XY:

117324

show subpopulations

Gnomad AFR exome

AF:

0.0000765

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000756

Gnomad NFE exome

AF:

0.000876

Gnomad OTH exome

AF:

0.00129

GnomAD4 exome

AF:

0.000455

AC:

657

AN:

1444820

Hom.:

Cov.:

AF XY:

0.000413

AC XY:

296

AN XY:

716804

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.0000473

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.000697

Gnomad4 NFE exome

AF:

0.000528

Gnomad4 OTH exome

AF:

0.000569

GnomAD4 genome

AF:

0.000368

AC:

AN:

152044

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.000648

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000722

Hom.:

Bravo

AF:

0.000385

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000646

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2024

The c.529G>A (p.E177K) alteration is located in exon 6 (coding exon 6) of the ARID5A gene. This alteration results from a G to A substitution at nucleotide position 529, causing the glutamic acid (E) at amino acid position 177 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.055

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.76

N;N

REVEL

Benign

0.12

Sift

Benign

0.12

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.64

P;.

Vest4

0.17

MVP

0.55

MPC

0.66

ClinPred

0.047

GERP RS

4.7

Varity_R

0.12

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over