chr20-45314534-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_014276.4(RBPJL):c.989G>A(p.Cys330Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
RBPJL
NM_014276.4 missense
NM_014276.4 missense
Scores
8
7
3
Clinical Significance
Conservation
PhyloP100: 9.51
Genes affected
RBPJL (HGNC:13761): (recombination signal binding protein for immunoglobulin kappa J region like) This gene encodes a member of the suppressor of hairless protein family. A similar protein in mouse is a transcription factor that binds to DNA sequences almost identical to that bound by the Notch receptor signaling pathway transcription factor recombining binding protein J. The mouse protein has been shown to activate transcription in concert with Epstein-Barr virus nuclear antigen-2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.963
BS2
High AC in GnomAdExome4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBPJL | NM_014276.4 | c.989G>A | p.Cys330Tyr | missense_variant | 9/12 | ENST00000343694.8 | |
RBPJL | NM_001281449.2 | c.989G>A | p.Cys330Tyr | missense_variant | 9/12 | ||
RBPJL | NM_001281448.2 | c.989G>A | p.Cys330Tyr | missense_variant | 9/12 | ||
RBPJL | XM_011528522.3 | c.989G>A | p.Cys330Tyr | missense_variant | 9/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBPJL | ENST00000343694.8 | c.989G>A | p.Cys330Tyr | missense_variant | 9/12 | 1 | NM_014276.4 | A1 | |
RBPJL | ENST00000372743.5 | c.989G>A | p.Cys330Tyr | missense_variant | 9/12 | 1 | P4 | ||
RBPJL | ENST00000372741.7 | c.989G>A | p.Cys330Tyr | missense_variant | 9/12 | 1 | |||
RBPJL | ENST00000464504.2 | c.233G>A | p.Cys78Tyr | missense_variant | 2/5 | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251206Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135780
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461698Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727134
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
ExAC
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1
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 | Dec 16, 2023 | The c.989G>A (p.C330Y) alteration is located in exon 9 (coding exon 9) of the RBPJL gene. This alteration results from a G to A substitution at nucleotide position 989, causing the cysteine (C) at amino acid position 330 to be replaced by a tyrosine (Y). 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
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
1.0
.;D;D
Vest4
MutPred
Loss of catalytic residue at L331 (P = 0.0189);Loss of catalytic residue at L331 (P = 0.0189);Loss of catalytic residue at L331 (P = 0.0189);
MVP
MPC
1.6
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at