15-74543949-C-G

Position:

• chr15-74543949-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_006465.4(ARID3B):​c.13C>G​(p.Gln5Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: ARID3B NM_006465.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75

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 1 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=0.083910435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID3B	NM_006465.4	c.13C>G	p.Gln5Glu	missense_variant	2/9	ENST00000346246.10
ARID3B	NM_001307939.2	c.13C>G	p.Gln5Glu	missense_variant	2/9
ARID3B	XR_007064418.1	n.90C>G		non_coding_transcript_exon_variant	1/9
ARID3B	XR_007064419.1	n.90C>G		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID3B	ENST00000346246.10	c.13C>G	p.Gln5Glu	missense_variant	2/9	1	NM_006465.4	P4
ARID3B	ENST00000622429.1	c.13C>G	p.Gln5Glu	missense_variant	2/9	1		A2
ARID3B	ENST00000569680.1	n.157C>G		non_coding_transcript_exon_variant	2/4	1

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

May 11, 2022

The c.13C>G (p.Q5E) alteration is located in exon 2 (coding exon 1) of the ARID3B gene. This alteration results from a C to G substitution at nucleotide position 13, causing the glutamine (Q) at amino acid position 5 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	Benign	0.084
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.50
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.77
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.35	T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.74	N;.
REVEL	Benign	0.084
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.13	T;T
Polyphen		0.030	B;B
Vest4		0.30
MutPred		0.098		Loss of glycosylation at P3 (P = 0.1493);Loss of glycosylation at P3 (P = 0.1493);
MVP		0.068
MPC		0.72
ClinPred		0.31	T
GERP RS		1.6
Varity_R		0.042
gMVP		0.20

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

Other links and lift over

dbSNP: rs751127718; hg19: chr15-74836290;