Variant rs188867560 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_005089.4(ZRSR2):c.283G>A(p.Ala95Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000529 in 1,193,897 control chromosomes in the GnomAD database, including 4 homozygotes. There are 178 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.00051 ( 1 hom., 16 hem., cov: 22)

Exomes 𝑓: 0.00053 ( 3 hom. 162 hem. )

Consequence

ZRSR2
NM_005089.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 4.67

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:

ZRSR2 (HGNC:):

ZRSR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044573843).

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000531 (575/1083604) while in subpopulation EAS AF= 0.0166 (491/29652). AF 95% confidence interval is 0.0153. There are 3 homozygotes in gnomad4_exome. There are 162 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Hemizygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRSR2	NM_005089.4 linkuse as main transcript	c.283G>A	p.Ala95Thr	missense_variant	4/11	ENST00000307771.8	NP_005080.1	Q15696
ZRSR2	XM_011545589.4 linkuse as main transcript	c.352G>A	p.Ala118Thr	missense_variant	3/10		XP_011543891.3	A0A8I5KSD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRSR2	ENST00000307771.8 linkuse as main transcript	c.283G>A	p.Ala95Thr	missense_variant	4/11	1	NM_005089.4	ENSP00000303015.7		Q15696

Frequencies

GnomAD3 genomes

AF:

0.000517

AC:

AN:

110239

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

32461

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000983

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00162

AC:

254

AN:

156370

Hom.:

AF XY:

0.00133

AC XY:

AN XY:

48738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000400

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0202

Gnomad SAS exome

AF:

0.000311

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000977

GnomAD4 exome

AF:

0.000531

AC:

575

AN:

1083604

Hom.:

Cov.:

AF XY:

0.000459

AC XY:

162

AN XY:

353122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000298

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0166

Gnomad4 SAS exome

AF:

0.000404

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.000508

AC:

AN:

110293

Hom.:

Cov.:

AF XY:

0.000492

AC XY:

AN XY:

32525

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000982

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0156

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000789

Hom.:

Bravo

AF:

0.000631

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00151

AC:

182

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0045

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.34

Sift

Benign

0.20

Sift4G

Benign

0.26

Polyphen

0.20

Vest4

0.12

MVP

0.72

MPC

0.39

ClinPred

0.023

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.13

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.

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