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GeneBe

X-15820288-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005089.4(ZRSR2):c.909C>T(p.Pro303=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,209,204 control chromosomes in the GnomAD database, including 78 homozygotes. There are 4,487 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0089 ( 4 hom., 276 hem., cov: 23)
Exomes 𝑓: 0.012 ( 74 hom. 4211 hem. )

Consequence

ZRSR2
NM_005089.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.16
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 -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-15820288-C-T is Benign according to our data. Variant chrX-15820288-C-T is described in ClinVar as [Benign]. Clinvar id is 773378.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-15820288-C-T is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.16 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZRSR2NM_005089.4 linkuse as main transcriptc.909C>T p.Pro303= synonymous_variant 10/11 ENST00000307771.8
ZRSR2XM_011545589.4 linkuse as main transcriptc.978C>T p.Pro326= synonymous_variant 9/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZRSR2ENST00000307771.8 linkuse as main transcriptc.909C>T p.Pro303= synonymous_variant 10/111 NM_005089.4 P2
ZRSR2ENST00000684799.1 linkuse as main transcriptc.831C>T p.Pro277= synonymous_variant 9/11 A2
ZRSR2ENST00000690252.1 linkuse as main transcriptc.909C>T p.Pro303= synonymous_variant, NMD_transcript_variant 10/13
ZRSR2ENST00000691502.1 linkuse as main transcriptc.909C>T p.Pro303= synonymous_variant, NMD_transcript_variant 10/13

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00890
AC:
996
AN:
111863
Hom.:
4
Cov.:
23
AF XY:
0.00811
AC XY:
276
AN XY:
34033
show subpopulations
Gnomad AFR
AF:
0.00172
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0104
Gnomad ASJ
AF:
0.00452
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00299
Gnomad FIN
AF:
0.00746
Gnomad MID
AF:
0.0294
Gnomad NFE
AF:
0.0139
Gnomad OTH
AF:
0.0140
GnomAD3 exomes
AF:
0.00872
AC:
1593
AN:
182784
Hom.:
9
AF XY:
0.00843
AC XY:
567
AN XY:
67244
show subpopulations
Gnomad AFR exome
AF:
0.00137
Gnomad AMR exome
AF:
0.00707
Gnomad ASJ exome
AF:
0.00790
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00100
Gnomad FIN exome
AF:
0.00887
Gnomad NFE exome
AF:
0.0136
Gnomad OTH exome
AF:
0.0109
GnomAD4 exome
AF:
0.0118
AC:
12921
AN:
1097293
Hom.:
74
Cov.:
30
AF XY:
0.0116
AC XY:
4211
AN XY:
362681
show subpopulations
Gnomad4 AFR exome
AF:
0.00193
Gnomad4 AMR exome
AF:
0.00745
Gnomad4 ASJ exome
AF:
0.00805
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00102
Gnomad4 FIN exome
AF:
0.00874
Gnomad4 NFE exome
AF:
0.0136
Gnomad4 OTH exome
AF:
0.0123
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00887
AC:
993
AN:
111911
Hom.:
4
Cov.:
23
AF XY:
0.00810
AC XY:
276
AN XY:
34093
show subpopulations
Gnomad4 AFR
AF:
0.00172
Gnomad4 AMR
AF:
0.0104
Gnomad4 ASJ
AF:
0.00452
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00262
Gnomad4 FIN
AF:
0.00746
Gnomad4 NFE
AF:
0.0139
Gnomad4 OTH
AF:
0.0138
Alfa
AF:
0.00961
Hom.:
65
Bravo
AF:
0.00849
EpiCase
AF:
0.0152
EpiControl
AF:
0.0169

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 24, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
0.87
Dann
Benign
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs148608893; hg19: chrX-15838411; COSMIC: COSV57063563; API