3-29434900-T-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001003793.3(RBMS3):c.233T>A(p.Ile78Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00062 in 1,613,558 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00064 ( 0 hom. )
Consequence
RBMS3
NM_001003793.3 missense
NM_001003793.3 missense
Scores
4
6
9
Clinical Significance
Conservation
PhyloP100: 8.02
Genes affected
RBMS3 (HGNC:13427): (RNA binding motif single stranded interacting protein 3) This gene encodes an RNA-binding protein that belongs to the c-myc gene single-strand binding protein family. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. These proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis. The encoded protein was isolated by virtue of its binding to an upstream element of the alpha2(I) collagen promoter. The observation that this protein localizes mostly in the cytoplasm suggests that it may be involved in a cytoplasmic function such as controlling RNA metabolism, rather than transcription. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RBMS3 | NM_001003793.3 | c.233T>A | p.Ile78Asn | missense_variant | 2/15 | ENST00000383767.7 | NP_001003793.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RBMS3 | ENST00000383767.7 | c.233T>A | p.Ile78Asn | missense_variant | 2/15 | 1 | NM_001003793.3 | ENSP00000373277.2 | ||
ENSG00000283563 | ENST00000635992.1 | n.*740T>A | non_coding_transcript_exon_variant | 9/14 | 5 | ENSP00000489994.1 | ||||
ENSG00000283563 | ENST00000635992.1 | n.*740T>A | 3_prime_UTR_variant | 9/14 | 5 | ENSP00000489994.1 |
Frequencies
GnomAD3 genomes AF: 0.000388 AC: 59AN: 152120Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000214 AC: 53AN: 247948Hom.: 0 AF XY: 0.000231 AC XY: 31AN XY: 134180
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GnomAD4 exome AF: 0.000644 AC: 941AN: 1461320Hom.: 0 Cov.: 30 AF XY: 0.000619 AC XY: 450AN XY: 726930
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GnomAD4 genome AF: 0.000388 AC: 59AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74426
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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 | Sep 30, 2024 | The c.233T>A (p.I78N) alteration is located in exon 2 (coding exon 2) of the RBMS3 gene. This alteration results from a T to A substitution at nucleotide position 233, causing the isoleucine (I) at amino acid position 78 to be replaced by an asparagine (N). 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
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;.;N;.;N;N
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;T;D
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
0.82, 0.79, 0.11
.;P;.;.;P;.;B
Vest4
MVP
MPC
1.4
ClinPred
T
GERP RS
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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