15-74544439-T-C

Position:

chr15-74544439-T-C

Variant summary

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

The NM_006465.4(ARID3B):c.503T>C(p.Val168Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,930 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

ARID3B
NM_006465.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.845

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=0.0381082).

BS2

High AC in GnomAdExome4 at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID3B	NM_006465.4 linkuse as main transcript	c.503T>C	p.Val168Ala	missense_variant	2/9	ENST00000346246.10	NP_006456.1	Q8IVW6-4
ARID3B	NM_001307939.2 linkuse as main transcript	c.503T>C	p.Val168Ala	missense_variant	2/9		NP_001294868.1	Q8IVW6-1
ARID3B	XR_007064418.1 linkuse as main transcript	n.580T>C		non_coding_transcript_exon_variant	1/9
ARID3B	XR_007064419.1 linkuse as main transcript	n.580T>C		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARID3B	ENST00000346246.10 linkuse as main transcript	c.503T>C	p.Val168Ala	missense_variant	2/9	1	NM_006465.4	ENSP00000343126.5	Q8IVW6-4
ARID3B	ENST00000622429.1 linkuse as main transcript	c.503T>C	p.Val168Ala	missense_variant	2/9	1		ENSP00000477878.1	Q8IVW6-1
ARID3B	ENST00000569680.1 linkuse as main transcript	n.647T>C		non_coding_transcript_exon_variant	2/4	1
ARID3B	ENST00000566147.1 linkuse as main transcript	c.-76T>C		5_prime_UTR_variant	1/3	3		ENSP00000455668.1	H3BQ92

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727246

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:

0.0000432

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

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:

0.0000564

Hom.:

Bravo

AF:

0.00000756

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

Sep 25, 2024

The c.503T>C (p.V168A) alteration is located in exon 2 (coding exon 1) of the ARID3B gene. This alteration results from a T to C substitution at nucleotide position 503, causing the valine (V) at amino acid position 168 to be replaced by an alanine (A). 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

0.070

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

4.1

DANN

Benign

0.91

DEOGEN2

Benign

0.036

.;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.0093

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.43

PROVEAN

Benign

0.35

N;.

REVEL

Benign

0.023

Sift

Benign

0.63

T;.

Sift4G

Benign

0.98

T;T

Polyphen

0.018

B;B

Vest4

0.073

MutPred

0.19

Gain of glycosylation at P166 (P = 0.07);Gain of glycosylation at P166 (P = 0.07);

MVP

0.39

MPC

0.80

ClinPred

0.18

GERP RS

3.1

Varity_R

0.083

gMVP

0.16

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