Variant 15-74544097-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_006465.4(ARID3B):c.161C>T(p.Ser54Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ARID3B
NM_006465.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.10

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, ARID3B

BP4

Computational evidence support a benign effect (MetaRNN=0.33592892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ARID3B	NM_006465.4 linkuse as main transcript	c.161C>T	p.Ser54Phe	missense_variant	2/9	ENST00000346246.10
ARID3B	NM_001307939.2 linkuse as main transcript	c.161C>T	p.Ser54Phe	missense_variant	2/9
ARID3B	XR_007064418.1 linkuse as main transcript	n.238C>T		non_coding_transcript_exon_variant	1/9
ARID3B	XR_007064419.1 linkuse as main transcript	n.238C>T		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID3B	ENST00000346246.10 linkuse as main transcript	c.161C>T	p.Ser54Phe	missense_variant	2/9	1	NM_006465.4	P4	Q8IVW6-4
ARID3B	ENST00000622429.1 linkuse as main transcript	c.161C>T	p.Ser54Phe	missense_variant	2/9	1		A2	Q8IVW6-1
ARID3B	ENST00000569680.1 linkuse as main transcript	n.305C>T		non_coding_transcript_exon_variant	2/4	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461666

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Feb 16, 2023

The c.161C>T (p.S54F) alteration is located in exon 2 (coding exon 1) of the ARID3B gene. This alteration results from a C to T substitution at nucleotide position 161, causing the serine (S) at amino acid position 54 to be replaced by a phenylalanine (F). 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

0.14

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.8

N;.

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.99

D;D

Vest4

0.33

MVP

0.13

MPC

1.7

ClinPred

0.94

GERP RS

5.5

Varity_R

0.18

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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