Variant 14-58329539-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002892.4(ARID4A):c.674C>A(p.Ala225Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,447,598 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ARID4A
NM_002892.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

Variant links:

Genes affected

ARID4A (HGNC:9885): (AT-rich interaction domain 4A) The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein (pRB) which regulates cell proliferation. pRB represses transcription by recruiting the encoded protein. This protein, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function. The encoded protein possesses transcriptional repression activity. Multiple alternatively spliced transcripts have been observed for this gene, although not all transcript variants have been fully described. [provided by RefSeq, Jul 2008]

ARID4A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID4A	NM_002892.4 link	c.674C>A	p.Ala225Glu	missense_variant	Exon 10 of 24	ENST00000355431.8	NP_002883.3	P29374-1A0A024R657Q05CG0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID4A	ENST00000355431.8 link	c.674C>A	p.Ala225Glu	missense_variant	Exon 10 of 24	1	NM_002892.4	ENSP00000347602.3		P29374-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1447598

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721148

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:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.674C>A (p.A225E) alteration is located in exon 10 (coding exon 9) of the ARID4A gene. This alteration results from a C to A substitution at nucleotide position 674, causing the alanine (A) at amino acid position 225 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

Uncertain

0.46

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;.;.;T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D;D;D;.

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.65

D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M;M;.;M

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.0

N;N;N;N;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.012

D;D;D;D;D

Sift4G

Benign

0.078

T;T;T;D;T

Polyphen

0.64

P;D;B;.;D

Vest4

0.77

MutPred

0.72

Gain of catalytic residue at I224 (P = 0.0014);Gain of catalytic residue at I224 (P = 0.0014);Gain of catalytic residue at I224 (P = 0.0014);.;Gain of catalytic residue at I224 (P = 0.0014);

MVP

0.55

MPC

0.45

ClinPred

0.97

GERP RS

5.8

Varity_R

0.56

gMVP

0.60

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over