Variant 2-96550662-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_212481.3(ARID5A):c.499A>G(p.Lys167Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000043 in 1,605,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

ARID5A
NM_212481.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

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:

Genome browser will be placed here

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=0.11964947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID5A	NM_212481.3 linkuse as main transcript	c.499A>G	p.Lys167Glu	missense_variant	6/7	ENST00000357485.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID5A	ENST00000357485.8 linkuse as main transcript	c.499A>G	p.Lys167Glu	missense_variant	6/7	1	NM_212481.3	P1	Q03989-1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

151728

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000751

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000345

AC:

AN:

231968

Hom.:

AF XY:

0.0000239

AC XY:

AN XY:

125524

show subpopulations

Gnomad AFR exome

AF:

0.000423

Gnomad AMR exome

AF:

0.0000606

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000241

AC:

AN:

1453308

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

722012

show subpopulations

Gnomad4 AFR exome

AF:

0.000749

Gnomad4 AMR exome

AF:

0.0000687

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000999

GnomAD4 genome

AF:

0.000224

AC:

AN:

151844

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.000773

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000212

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

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

Oct 31, 2023

The c.499A>G (p.K167E) alteration is located in exon 6 (coding exon 6) of the ARID5A gene. This alteration results from a A to G substitution at nucleotide position 499, causing the lysine (K) at amino acid position 167 to be replaced by a glutamic acid (E). 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

0.29

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.23

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.045

T;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.055

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.61

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.022

D;D

Sift4G

Benign

0.21

T;T

Polyphen

0.24

B;.

Vest4

0.27

MVP

0.65

MPC

0.59

ClinPred

0.17

GERP RS

4.8

Varity_R

0.15

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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