Variant 15-74572877-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2

The NM_006465.4(ARID3B):c.568T>C(p.Trp190Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000527 in 1,614,076 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 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

ARID3B
NM_006465.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.72

Variant links:

Genes affected

ARID3B (HGNC:14350): (AT-rich interaction domain 3B) This gene encodes a member of the ARID (AT-rich interaction domain) family of DNA-binding proteins. The encoded protein is homologous with two proteins that bind to the retinoblastoma gene product, and also with the mouse Bright and Drosophila dead ringer proteins. A pseudogene on chromosome 1p31 exists for this gene. Members of the ARID family have roles in embryonic patterning, cell lineage gene regulation, cell cycle control, transcriptional regulation and possibly in chromatin structure modification. [provided by RefSeq, Jul 2008]

ARID3B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP2

Missense variant where missense usually causes diseases, ARID3B

BP4

Computational evidence support a benign effect (MetaRNN=0.38878974).

BS2

High AC in GnomAdExome4 at 81 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ARID3B	NM_006465.4 linkuse as main transcript	c.568T>C	p.Trp190Arg	missense_variant	3/9	ENST00000346246.10
ARID3B	NM_001307939.2 linkuse as main transcript	c.568T>C	p.Trp190Arg	missense_variant	3/9
ARID3B	XR_007064418.1 linkuse as main transcript	n.645T>C		non_coding_transcript_exon_variant	2/9
ARID3B	XR_007064419.1 linkuse as main transcript	n.645T>C		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID3B	ENST00000346246.10 linkuse as main transcript	c.568T>C	p.Trp190Arg	missense_variant	3/9	1	NM_006465.4	P4	Q8IVW6-4
ARID3B	ENST00000622429.1 linkuse as main transcript	c.568T>C	p.Trp190Arg	missense_variant	3/9	1		A2	Q8IVW6-1
ARID3B	ENST00000569680.1 linkuse as main transcript	n.712T>C		non_coding_transcript_exon_variant	3/4	1
ARID3B	ENST00000566147.1 linkuse as main transcript	c.-26-16943T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000107

AC:

AN:

251448

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000554

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00203

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000247

Hom.:

Bravo

AF:

0.0000529

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

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

Jul 13, 2022

The c.568T>C (p.W190R) alteration is located in exon 3 (coding exon 2) of the ARID3B gene. This alteration results from a T to C substitution at nucleotide position 568, causing the tryptophan (W) at amino acid position 190 to be replaced by an arginine (R). 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

Pathogenic

0.78

BayesDel_addAF

Uncertain

0.083

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.0

D;.

REVEL

Benign

0.27

Sift

Uncertain

0.0070

D;.

Sift4G

Uncertain

0.034

D;D

Polyphen

1.0

D;D

Vest4

0.72

MutPred

0.38

Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);

MVP

0.38

MPC

2.2

ClinPred

0.89

GERP RS

6.0

Varity_R

0.34

gMVP

0.46

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