chr15-74572931-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
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
NM_006465.4 missense, splice_region
Scores
3
9
6
Splicing: ADA: 0.7821
2
Clinical Significance
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]
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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;
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
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
D;P
Vest4
MutPred
Loss of ubiquitination at K208 (P = 0.0087);Loss of ubiquitination at K208 (P = 0.0087);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.