chrX-15823090-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_005089.4(ZRSR2):c.1297C>T(p.Arg433Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,206,610 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )
Consequence
ZRSR2
NM_005089.4 missense
NM_005089.4 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 0.159
Genes affected
ZRSR2 (HGNC:23019): (zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2) This gene encodes an essential splicing factor. The encoded protein associates with the U2 auxiliary factor heterodimer, which is required for the recognition of a functional 3' splice site in pre-mRNA splicing, and may play a role in network interactions during spliceosome assembly. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.10197902).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZRSR2 | NM_005089.4 | c.1297C>T | p.Arg433Cys | missense_variant | 11/11 | ENST00000307771.8 | |
ZRSR2 | XM_011545589.4 | c.1366C>T | p.Arg456Cys | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZRSR2 | ENST00000307771.8 | c.1297C>T | p.Arg433Cys | missense_variant | 11/11 | 1 | NM_005089.4 | P2 | |
ZRSR2 | ENST00000684799.1 | c.1219C>T | p.Arg407Cys | missense_variant | 10/11 | A2 | |||
ZRSR2 | ENST00000690252.1 | c.1297C>T | p.Arg433Cys | missense_variant, NMD_transcript_variant | 11/13 | ||||
ZRSR2 | ENST00000691502.1 | c.1183C>T | p.Arg395Cys | missense_variant, NMD_transcript_variant | 11/13 |
Frequencies
GnomAD3 genomes AF: 0.0000179 AC: 2AN: 111473Hom.: 0 Cov.: 23 AF XY: 0.0000594 AC XY: 2AN XY: 33683
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GnomAD4 exome AF: 0.00000183 AC: 2AN: 1095087Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 1AN XY: 360849
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GnomAD4 genome AF: 0.00000897 AC: 1AN: 111523Hom.: 0 Cov.: 23 AF XY: 0.0000296 AC XY: 1AN XY: 33743
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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 | Apr 25, 2023 | The c.1297C>T (p.R433C) alteration is located in exon 11 (coding exon 11) of the ZRSR2 gene. This alteration results from a C to T substitution at nucleotide position 1297, causing the arginine (R) at amino acid position 433 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of methylation at R433 (P = 0.0355);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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