Genetic Variant ZRSR2:p.Thr51Pro (chrX-15799901-A-C) – 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.151A>C(p.Thr51Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T51A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

ZRSR2
NM_005089.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.208

Publications

0 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=0.030752152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZRSR2	NM_005089.4 link	c.151A>C	p.Thr51Pro	missense_variant	Exon 3 of 11	ENST00000307771.8	NP_005080.1	Q15696
ZRSR2	XM_011545589.4 link	c.220A>C	p.Thr74Pro	missense_variant	Exon 2 of 10		XP_011543891.3	A0A8I5KSD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZRSR2	ENST00000307771.8 link	c.151A>C	p.Thr51Pro	missense_variant	Exon 3 of 11	1	NM_005089.4	ENSP00000303015.7		Q15696

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000556

AC:

AN:

179864

AF XY:

0.0000155

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000376

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

Data not reliable, filtered out with message: AS_VQSR

AF:

9.16e-7

AC:

AN:

1091460

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

357482

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26244

American (AMR)

AF:

0.0000286

AC:

AN:

35008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19272

East Asian (EAS)

AF:

0.00

AC:

AN:

30027

South Asian (SAS)

AF:

0.00

AC:

AN:

53340

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4114

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

837185

Other (OTH)

AF:

0.00

AC:

AN:

45854

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.4

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.0098

.;T

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.32

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.63

.;N

PhyloP100

-0.21

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.59

N;N

REVEL

Benign

0.084

Sift

Benign

0.23

.;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0

.;B

Vest4

0.13

MutPred

0.11

Loss of phosphorylation at T51 (P = 0.013);Loss of phosphorylation at T51 (P = 0.013);

MVP

0.14

MPC

0.53

ClinPred

0.029

GERP RS

-2.3

Varity_R

0.16

gMVP

0.39

Mutation Taster

=95/5

polymorphism

(source)

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

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X-15799901-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over