chrX-107069280-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001324242.2(RBM41):​c.1122G>C​(p.Arg374Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Consequence

RBM41
NM_001324242.2 missense

Scores

3
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.457
Variant links:
Genes affected
RBM41 (HGNC:25617): (RNA binding motif protein 41) Predicted to enable U12 snRNA binding activity and pre-mRNA intronic binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be part of U12-type spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.941

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBM41NM_001324242.2 linkc.1122G>C p.Arg374Ser missense_variant Exon 7 of 8 ENST00000685964.1 NP_001311171.1 A0A8I5KYC8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBM41ENST00000685964.1 linkc.1122G>C p.Arg374Ser missense_variant Exon 7 of 8 NM_001324242.2 ENSP00000509650.1 A0A8I5KYC8

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1050G>C (p.R350S) alteration is located in exon 6 (coding exon 6) of the RBM41 gene. This alteration results from a G to C substitution at nucleotide position 1050, causing the arginine (R) at amino acid position 350 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
0.82
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
.;T
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Pathogenic
0.43
D
MetaRNN
Pathogenic
0.94
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;M
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-4.0
D;D
REVEL
Benign
0.23
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.010
D;D
Polyphen
0.88
.;P
Vest4
0.82
MutPred
0.79
Loss of methylation at R350 (P = 0.0087);Loss of methylation at R350 (P = 0.0087);
MVP
0.64
MPC
0.67
ClinPred
0.98
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.72
gMVP
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: chrX-106312510; API