chrX-15790512-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005089.4(ZRSR2):ā€‹c.17A>Cā€‹(p.Lys6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,158,629 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000089 ( 0 hom., 0 hem., cov: 24)
Exomes š‘“: 0.000029 ( 0 hom. 13 hem. )

Consequence

ZRSR2
NM_005089.4 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.73
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0531635).
BS2
High Hemizygotes in GnomAdExome4 at 13 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZRSR2NM_005089.4 linkuse as main transcriptc.17A>C p.Lys6Thr 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 linkuse as main transcriptc.17A>C p.Lys6Thr missense_variant 1/111 NM_005089.4 ENSP00000303015.7 Q15696

Frequencies

GnomAD3 genomes
AF:
0.00000893
AC:
1
AN:
111969
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34153
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000287
AC:
30
AN:
1046660
Hom.:
0
Cov.:
31
AF XY:
0.0000383
AC XY:
13
AN XY:
339296
show subpopulations
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:
0.0000367
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000893
AC:
1
AN:
111969
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34153
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 03, 2024The c.17A>C (p.K6T) alteration is located in exon 1 (coding exon 1) of the ZRSR2 gene. This alteration results from a A to C substitution at nucleotide position 17, causing the lysine (K) at amino acid position 6 to be replaced by a threonine (T). 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
0.061
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.038
DANN
Benign
0.64
DEOGEN2
Benign
0.015
.;T
FATHMM_MKL
Benign
0.025
N
LIST_S2
Benign
0.25
T;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.053
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
.;L
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.040
N;N
REVEL
Benign
0.025
Sift
Benign
0.46
.;T
Sift4G
Benign
0.42
T;T
Polyphen
0.0
.;B
Vest4
0.12
MutPred
0.17
Loss of ubiquitination at K6 (P = 0.0043);Loss of ubiquitination at K6 (P = 0.0043);
MVP
0.15
MPC
0.49
ClinPred
0.082
T
GERP RS
-11
Varity_R
0.074
gMVP
0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1198313061; hg19: chrX-15808635; API