dbSNP rs188867560: ZRSR2:p.Ala95Thr (chrX-15803767-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -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. 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

Publications

8 publications found

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 was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

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

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 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 GnomAdExome4. There are 162 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check. 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 rank	MANE	Protein	UniProt
ZRSR2	NM_005089.4 link	c.283G>A	p.Ala95Thr	missense_variant	Exon 4 of 11	ENST00000307771.8	NP_005080.1	Q15696
ZRSR2	XM_011545589.4 link	c.352G>A	p.Ala118Thr	missense_variant	Exon 3 of 10		XP_011543891.3	A0A8I5KSD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZRSR2	ENST00000307771.8 link	c.283G>A	p.Ala95Thr	missense_variant	Exon 4 of 11	1	NM_005089.4	ENSP00000303015.7		Q15696

Frequencies

GnomAD3 genomes

AF:

0.000517

AC:

AN:

110239

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00162

AC:

254

AN:

156370

AF XY:

0.00133

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 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

African (AFR)

AF:

0.00

AC:

AN:

25978

American (AMR)

AF:

0.0000298

AC:

AN:

33538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19151

East Asian (EAS)

AF:

0.0166

AC:

491

AN:

29652

South Asian (SAS)

AF:

0.000404

AC:

AN:

51947

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4123

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

833921

Other (OTH)

AF:

0.00129

AC:

AN:

45586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000508

AC:

AN:

110293

Hom.:

Cov.:

AF XY:

0.000492

AC XY:

AN XY:

32525

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30314

American (AMR)

AF:

0.0000982

AC:

AN:

10188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.0156

AC:

AN:

3535

South Asian (SAS)

AF:

0.00

AC:

AN:

2590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5721

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52913

Other (OTH)

AF:

0.00

AC:

AN:

1492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000734

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

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

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

(source)

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

PhyloP100

4.7

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

Mutation Taster

=90/10

polymorphism (auto)

(source)

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

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rs188867560

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over