20-422150-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031229.4(RBCK1):​c.941G>T​(p.Arg314Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RBCK1
NM_031229.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01
Variant links:
Genes affected
RBCK1 (HGNC:15864): (RANBP2-type and C3HC4-type zinc finger containing 1) Enables several functions, including identical protein binding activity; protein sequestering activity; and ubiquitin binding activity. Involved in several processes, including T cell receptor signaling pathway; cellular protein metabolic process; and regulation of DNA-binding transcription factor activity. Part of LUBAC complex. Implicated in glycogen storage disease. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07819578).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBCK1NM_031229.4 linkc.941G>T p.Arg314Leu missense_variant Exon 8 of 12 ENST00000356286.10 NP_112506.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBCK1ENST00000356286.10 linkc.941G>T p.Arg314Leu missense_variant Exon 8 of 12 1 NM_031229.4 ENSP00000348632.6 Q9BYM8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460350
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726374
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:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T;.;.;.
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.85
T;D;D;.
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.078
T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.56
N;.;.;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.82
N;.;N;N
REVEL
Benign
0.063
Sift
Benign
1.0
T;.;T;T
Sift4G
Benign
0.39
T;.;T;T
Polyphen
0.0
B;B;B;B
Vest4
0.20
MutPred
0.49
Loss of disorder (P = 0.0583);.;.;.;
MVP
0.52
MPC
0.52
ClinPred
0.16
T
GERP RS
3.0
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.2
Varity_R
0.076
gMVP
0.61

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: chr20-402794; API