Genetic Variant ZRSR2:p.Val250Met (chrX-15815867-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005089.4(ZRSR2):c.748G>A(p.Val250Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000664 in 1,205,528 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 1 hem. )

Consequence

ZRSR2
NM_005089.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 6.54

Publications

2 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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32459497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZRSR2	NM_005089.4 link	c.748G>A	p.Val250Met	missense_variant	Exon 8 of 11	ENST00000307771.8	NP_005080.1	Q15696
ZRSR2	XM_011545589.4 link	c.817G>A	p.Val273Met	missense_variant	Exon 7 of 10		XP_011543891.3	A0A8I5KSD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZRSR2	ENST00000307771.8 link	c.748G>A	p.Val250Met	missense_variant	Exon 8 of 11	1	NM_005089.4	ENSP00000303015.7	Q15696
ZRSR2	ENST00000684799.1 link	c.670G>A	p.Val224Met	missense_variant	Exon 7 of 11			ENSP00000510773.1	A0A8I5KSD0
ZRSR2	ENST00000690252.1 link	n.748G>A		non_coding_transcript_exon_variant	Exon 8 of 13			ENSP00000510140.1	A0A8I5KRH1
ZRSR2	ENST00000691502.1 link	n.748G>A		non_coding_transcript_exon_variant	Exon 8 of 13			ENSP00000509336.1	A0A8I5QKS0

Frequencies

GnomAD3 genomes

AF:

0.0000361

AC:

AN:

110919

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000985

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000112

AC:

AN:

178274

AF XY:

0.0000159

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000457

AC:

AN:

1094556

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

360150

show subpopulations

African (AFR)

AF:

0.000114

AC:

AN:

26374

American (AMR)

AF:

0.00

AC:

AN:

35000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19146

East Asian (EAS)

AF:

0.00

AC:

AN:

30158

South Asian (SAS)

AF:

0.00

AC:

AN:

53463

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40379

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4119

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

839962

Other (OTH)

AF:

0.00

AC:

AN:

45955

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000270

AC:

AN:

110972

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33188

show subpopulations

African (AFR)

AF:

0.0000655

AC:

AN:

30523

American (AMR)

AF:

0.00

AC:

AN:

10397

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2630

East Asian (EAS)

AF:

0.00

AC:

AN:

3528

South Asian (SAS)

AF:

0.00

AC:

AN:

2602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5893

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

53002

Other (OTH)

AF:

0.00

AC:

AN:

1495

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

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

0.24

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.027

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.32

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.1

PhyloP100

6.5

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.1

REVEL

Benign

0.26

Sift

Benign

0.046

Sift4G

Benign

0.15

Polyphen

1.0

Vest4

0.39

MutPred

0.61

Gain of catalytic residue at V250 (P = 0.0594);

MVP

0.51

MPC

1.2

ClinPred

0.58

GERP RS

5.4

Varity_R

0.38

gMVP

0.76

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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X-15815867-G-A

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