Variant 10-62057275-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032199.3(ARID5B):c.1005G>C(p.Arg335Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARID5B
NM_032199.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

Variant links:

Genes affected

ARID5B (HGNC:17362): (AT-rich interaction domain 5B) This gene encodes a member of the AT-rich interaction domain (ARID) family of DNA binding proteins. The encoded protein forms a histone H3K9Me2 demethylase complex with PHD finger protein 2 and regulates the transcription of target genes involved in adipogenesis and liver development. This gene also plays a role in cell growth and differentiation of B-lymphocyte progenitors, and single nucleotide polymorphisms in this gene are associated with acute lymphoblastic leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

ARID5B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID5B	NM_032199.3 linkuse as main transcript	c.1005G>C	p.Arg335Ser	missense_variant	6/10	ENST00000279873.12
ARID5B	NM_001244638.2 linkuse as main transcript	c.276G>C	p.Arg92Ser	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID5B	ENST00000279873.12 linkuse as main transcript	c.1005G>C	p.Arg335Ser	missense_variant	6/10	1	NM_032199.3	P3	Q14865-1
ARID5B	ENST00000681100.1 linkuse as main transcript	c.1005G>C	p.Arg335Ser	missense_variant	6/10
ARID5B	ENST00000309334.5 linkuse as main transcript	c.276G>C	p.Arg92Ser	missense_variant	3/7	5		A1	Q14865-2
ARID5B	ENST00000647323.1 linkuse as main transcript			downstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000732

AC:

AN:

1366620

Hom.:

Cov.:

AF XY:

0.00000588

AC XY:

AN XY:

680132

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:

0.000116

Gnomad4 NFE exome

AF:

0.00000285

Gnomad4 OTH exome

AF:

0.0000371

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.1005G>C (p.R335S) alteration is located in exon 6 (coding exon 6) of the ARID5B gene. This alteration results from a G to C substitution at nucleotide position 1005, causing the arginine (R) at amino acid position 335 to be replaced by a serine (S). 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

1.0

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.72

D;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Uncertain

-0.071

MutationAssessor

Pathogenic

3.0

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;D

Vest4

0.94

MutPred

0.57

Gain of ubiquitination at K336 (P = 0.0605);.;

MVP

0.95

MPC

3.2

ClinPred

1.0

GERP RS

3.1

Varity_R

0.88

gMVP

0.97

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

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