X-15790518-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005089.4(ZRSR2):​c.23C>A​(p.Thr8Lys) 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 benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control

Consequence

ZRSR2
NM_005089.4 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.218
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.057759225).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZRSR2NM_005089.4 linkc.23C>A p.Thr8Lys missense_variant 1/11 ENST00000307771.8 NP_005080.1 Q15696

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZRSR2ENST00000307771.8 linkc.23C>A p.Thr8Lys missense_variant 1/111 NM_005089.4 ENSP00000303015.7 Q15696

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1046911
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
339413
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:
0.00
Gnomad4 OTH exome
AF:
0.00
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 07, 2024The c.23C>A (p.T8K) alteration is located in exon 1 (coding exon 1) of the ZRSR2 gene. This alteration results from a C to A substitution at nucleotide position 23, causing the threonine (T) at amino acid position 8 to be replaced by a lysine (K). 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
Benign
0.076
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
1.1
DANN
Benign
0.48
DEOGEN2
Benign
0.013
.;T
FATHMM_MKL
Benign
0.059
N
LIST_S2
Benign
0.61
T;T
M_CAP
Benign
0.0080
T
MetaRNN
Benign
0.058
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.36
N;N
REVEL
Benign
0.0070
Sift
Benign
0.58
.;T
Sift4G
Benign
0.073
T;T
Polyphen
0.012
.;B
Vest4
0.089
MutPred
0.21
Loss of phosphorylation at T8 (P = 0.0099);Loss of phosphorylation at T8 (P = 0.0099);
MVP
0.068
MPC
0.49
ClinPred
0.063
T
GERP RS
-1.6
Varity_R
0.042
gMVP
0.17

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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-15808641; API