chr10-62085803-AC-A

Position:

• chr10-62085803-AC-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The ENST00000279873.12(ARID5B):​c.1302del​(p.Asn434LysfsTer45) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID5B ENST00000279873.12 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.122

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID5B	NM_032199.3	c.1302del	p.Asn434LysfsTer45	frameshift_variant	9/10	ENST00000279873.12	NP_115575.1
ARID5B	NM_001244638.2	c.573del	p.Asn191LysfsTer45	frameshift_variant	6/7		NP_001231567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID5B	ENST00000279873.12	c.1302del	p.Asn434LysfsTer45	frameshift_variant	9/10	1	NM_032199.3	ENSP00000279873	P3
ARID5B	ENST00000681100.1	c.1278del	p.Asn426LysfsTer45	frameshift_variant	9/10			ENSP00000506119
ARID5B	ENST00000309334.5	c.573del	p.Asn191LysfsTer45	frameshift_variant	6/7	5		ENSP00000308862	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fetal growth restriction;C0035353:Retrognathia;C0454644:Delayed speech and language development;C0542514:Blue sclerae;C0557874:Global developmental delay;C1578482:Pes valgus;C1837260:Prominent forehead;C4023408:Abnormality of mouth size Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

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Computational scores

Source: dbNSFP v4.3

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.

Other links and lift over

hg19: chr10-63845562; COSMIC: COSV105850463;