chrX-15823063-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005089.4(ZRSR2):c.1270G>C(p.Gly424Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 24)
Consequence
ZRSR2
NM_005089.4 missense
NM_005089.4 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 6.03
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.16564092).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZRSR2 | NM_005089.4 | c.1270G>C | p.Gly424Arg | missense_variant | 11/11 | ENST00000307771.8 | |
ZRSR2 | XM_011545589.4 | c.1339G>C | p.Gly447Arg | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZRSR2 | ENST00000307771.8 | c.1270G>C | p.Gly424Arg | missense_variant | 11/11 | 1 | NM_005089.4 | P2 | |
ZRSR2 | ENST00000684799.1 | c.1192G>C | p.Gly398Arg | missense_variant | 10/11 | A2 | |||
ZRSR2 | ENST00000690252.1 | c.1270G>C | p.Gly424Arg | missense_variant, NMD_transcript_variant | 11/13 | ||||
ZRSR2 | ENST00000691502.1 | c.1156G>C | p.Gly386Arg | missense_variant, NMD_transcript_variant | 11/13 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
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 | Aug 23, 2021 | The c.1270G>C (p.G424R) alteration is located in exon 11 (coding exon 11) of the ZRSR2 gene. This alteration results from a G to C substitution at nucleotide position 1270, causing the glycine (G) at amino acid position 424 to be replaced by an arginine (R). 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
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of loop (P = 0.0512);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.