Variant X-15820288-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005089.4(ZRSR2):c.909C>T(p.Pro303Pro) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

ZRSR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

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_multiple_submitters_no_conflicts, 2 stars. Variant chrX-15820288-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.16 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRSR2	NM_005089.4 linkuse as main transcript	c.909C>T	p.Pro303Pro	synonymous_variant	10/11	ENST00000307771.8	NP_005080.1	Q15696
ZRSR2	XM_011545589.4 linkuse as main transcript	c.978C>T	p.Pro326Pro	synonymous_variant	9/10		XP_011543891.3	A0A8I5KSD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZRSR2	ENST00000307771.8 linkuse as main transcript	c.909C>T	p.Pro303Pro	synonymous_variant	10/11	1	NM_005089.4	ENSP00000303015.7	Q15696
ZRSR2	ENST00000684799.1 linkuse as main transcript	c.831C>T	p.Pro277Pro	synonymous_variant	9/11			ENSP00000510773.1	A0A8I5KSD0
ZRSR2	ENST00000690252.1 linkuse as main transcript	n.909C>T		non_coding_transcript_exon_variant	10/13			ENSP00000510140.1	A0A8I5KRH1
ZRSR2	ENST00000691502.1 linkuse as main transcript	n.909C>T		non_coding_transcript_exon_variant	10/13			ENSP00000509336.1	A0A8I5QKS0

Frequencies

GnomAD3 genomes

AF:

0.00890

AC:

996

AN:

111863

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00887

AC:

993

AN:

111911

Hom.:

Cov.:

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.:

Bravo

AF:

0.00849

EpiCase

AF:

0.0152

EpiControl

AF:

0.0169

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over