15-74572931-A-G

Position:

• chr15-74572931-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_006465.4(ARID3B):​c.622A>G​(p.Lys208Glu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID3B NM_006465.4 missense, splice_region
• Scores: Splicing: ADA: 0.7821
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ARID3B

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID3B	NM_006465.4	c.622A>G	p.Lys208Glu	missense_variant, splice_region_variant	3/9	ENST00000346246.10
ARID3B	NM_001307939.2	c.622A>G	p.Lys208Glu	missense_variant, splice_region_variant	3/9
ARID3B	XR_007064418.1	n.699A>G		splice_region_variant, non_coding_transcript_exon_variant	2/9
ARID3B	XR_007064419.1	n.699A>G		splice_region_variant, non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID3B	ENST00000346246.10	c.622A>G	p.Lys208Glu	missense_variant, splice_region_variant	3/9	1	NM_006465.4	P4
ARID3B	ENST00000622429.1	c.622A>G	p.Lys208Glu	missense_variant, splice_region_variant	3/9	1		A2
ARID3B	ENST00000569680.1	n.766A>G		splice_region_variant, non_coding_transcript_exon_variant	3/4	1
ARID3B	ENST00000566147.1	c.-26-16889A>G		intron_variant		3

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

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2023

The c.622A>G (p.K208E) alteration is located in exon 3 (coding exon 2) of the ARID3B gene. This alteration results from a A to G substitution at nucleotide position 622, causing the lysine (K) at amino acid position 208 to be replaced by a glutamic acid (E). 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	0.95
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.3	N;.
REVEL	Benign	0.22
Sift	Uncertain	0.0080	D;.
Sift4G	Uncertain	0.018	D;D
Polyphen		0.99	D;P
Vest4		0.66
MutPred		0.38		Loss of ubiquitination at K208 (P = 0.0087);Loss of ubiquitination at K208 (P = 0.0087);
MVP		0.27
MPC		1.8
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.54
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.78
dbscSNV1_RF	Benign	0.51
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-74865272;