7-155680607-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_053043.3(RBM33):ā€‹c.266T>Gā€‹(p.Ile89Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000622 in 1,446,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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 š‘“: 0.0000062 ( 0 hom. )

Consequence

RBM33
NM_053043.3 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.24
Variant links:
Genes affected
RBM33 (HGNC:27223): (RNA binding motif protein 33) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3963481).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RBM33NM_053043.3 linkuse as main transcriptc.266T>G p.Ile89Ser missense_variant 5/18 ENST00000401878.8 NP_444271.2 Q96EV2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RBM33ENST00000401878.8 linkuse as main transcriptc.266T>G p.Ile89Ser missense_variant 5/185 NM_053043.3 ENSP00000384160.3 Q96EV2-1
RBM33ENST00000392759.7 linkuse as main transcriptc.266T>G p.Ile89Ser missense_variant 5/75 ENSP00000376513.3 A8MTF7
RBM33ENST00000287912.7 linkuse as main transcriptc.266T>G p.Ile89Ser missense_variant 5/62 ENSP00000287912.3 Q96EV2-2
RBM33ENST00000307403.6 linkuse as main transcriptn.131T>G non_coding_transcript_exon_variant 3/122 ENSP00000303878.2 H7BXM6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000622
AC:
9
AN:
1446836
Hom.:
0
Cov.:
32
AF XY:
0.00000974
AC XY:
7
AN XY:
718736
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:
0.00000814
Gnomad4 OTH exome
AF:
0.00
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 submitterclinical testingAmbry GeneticsSep 27, 2024The c.266T>G (p.I89S) alteration is located in exon 5 (coding exon 5) of the RBM33 gene. This alteration results from a T to G substitution at nucleotide position 266, causing the isoleucine (I) at amino acid position 89 to be replaced by a serine (S). 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
0.58
BayesDel_addAF
Benign
-0.053
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.065
.;T;.
Eigen
Benign
0.10
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.40
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L;L;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-4.5
D;N;D
REVEL
Benign
0.17
Sift
Uncertain
0.0020
D;D;D
Sift4G
Benign
0.070
T;D;T
Polyphen
0.95
P;P;.
Vest4
0.82
MutPred
0.065
Gain of phosphorylation at I89 (P = 0.0555);Gain of phosphorylation at I89 (P = 0.0555);Gain of phosphorylation at I89 (P = 0.0555);
MVP
0.18
MPC
1.9
ClinPred
0.96
D
GERP RS
5.7
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.38
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr7-155473301; API