15-74591311-G-A

Position:

chr15-74591311-G-A

Variant summary

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

The NM_006465.4(ARID3B):c.1042G>A(p.Ala348Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

ARID3B
NM_006465.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.396

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:

ARID3B (HGNC:):

ARID3B 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=0.020637512).

BS2

High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID3B	NM_006465.4 linkuse as main transcript	c.1042G>A	p.Ala348Thr	missense_variant	6/9	ENST00000346246.10	NP_006456.1	Q8IVW6-4
ARID3B	NM_001307939.2 linkuse as main transcript	c.1042G>A	p.Ala348Thr	missense_variant	6/9		NP_001294868.1	Q8IVW6-1
ARID3B	XR_007064418.1 linkuse as main transcript	n.1119G>A		non_coding_transcript_exon_variant	5/9
ARID3B	XR_007064419.1 linkuse as main transcript	n.1119G>A		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARID3B	ENST00000346246.10 linkuse as main transcript	c.1042G>A	p.Ala348Thr	missense_variant	6/9	1	NM_006465.4	ENSP00000343126.5	Q8IVW6-4
ARID3B	ENST00000622429.1 linkuse as main transcript	c.1042G>A	p.Ala348Thr	missense_variant	6/9	1		ENSP00000477878.1	Q8IVW6-1
ARID3B	ENST00000566468.1 linkuse as main transcript	n.125G>A		non_coding_transcript_exon_variant	1/2	1
ARID3B	ENST00000566147.1 linkuse as main transcript	c.319G>A	p.Ala107Thr	missense_variant	3/3	3		ENSP00000455668.1	H3BQ92

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000801

AC:

AN:

249670

Hom.:

AF XY:

0.0000886

AC XY:

AN XY:

135440

show subpopulations

Gnomad AFR exome

AF:

0.0000643

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000709

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1461574

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000707

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 29, 2024

The c.1042G>A (p.A348T) alteration is located in exon 6 (coding exon 5) of the ARID3B gene. This alteration results from a G to A substitution at nucleotide position 1042, causing the alanine (A) at amino acid position 348 to be replaced by a threonine (T). 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

0.069

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.69

DANN

Benign

0.80

DEOGEN2

Benign

0.039

.;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.51

T;T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.16

N;.;N

REVEL

Benign

0.049

Sift

Benign

0.36

T;.;T

Sift4G

Benign

0.85

T;T;T

Polyphen

0.0030

B;B;.

Vest4

0.16

MVP

0.49

MPC

0.64

ClinPred

0.025

GERP RS

-6.6

Varity_R

0.019

gMVP

0.43

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