dbSNP rs587778766: ZRSR2:p.Gly436Asp (chrX-15823100-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005089.4(ZRSR2):c.1307G>A(p.Gly436Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

ZRSR2
NM_005089.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 1.25

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048667222).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005089.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZRSR2	NM_005089.4	MANE Select	c.1307G>A	p.Gly436Asp	missense	Exon 11 of 11	NP_005080.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZRSR2	ENST00000307771.8	TSL:1 MANE Select	c.1307G>A	p.Gly436Asp	missense	Exon 11 of 11	ENSP00000303015.7
ZRSR2	ENST00000684799.1		c.1229G>A	p.Gly410Asp	missense	Exon 10 of 11	ENSP00000510773.1
ZRSR2	ENST00000690252.1		n.1307G>A		non_coding_transcript_exon	Exon 11 of 13	ENSP00000510140.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1093283

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

359777

African (AFR)

AF:

0.00

AC:

AN:

26270

American (AMR)

AF:

0.00

AC:

AN:

34775

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19255

East Asian (EAS)

AF:

0.00

AC:

AN:

30090

South Asian (SAS)

AF:

0.00

AC:

AN:

53808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39963

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3872

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

839402

Other (OTH)

AF:

0.00

AC:

AN:

45848

GnomAD4 genome

Cov.:

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.9

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.48

M_CAP

Benign

0.0099

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.5

PhyloP100

1.2

PrimateAI

Benign

0.35

PROVEAN

Benign

0.21

REVEL

Benign

0.012

Sift

Benign

0.22

Sift4G

Benign

0.55

Polyphen

0.11

Vest4

0.13

MVP

0.14

MPC

0.53

ClinPred

0.065

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.23

Mutation Taster

=93/7

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over