Genetic Variant NM_005089.4:c.23C>A (chrX-15790518-C-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.23C>A(p.Thr8Lys) 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 Uncertain significance (★).

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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.218

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=0.057759225).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZRSR2	NM_005089.4	MANE Select	c.23C>A	p.Thr8Lys	missense	Exon 1 of 11	NP_005080.1	Q15696

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZRSR2	ENST00000307771.8	TSL:1 MANE Select	c.23C>A	p.Thr8Lys	missense	Exon 1 of 11	ENSP00000303015.7	Q15696
ZRSR2	ENST00000380308.7	TSL:1	c.23C>A	p.Thr8Lys	missense	Exon 1 of 4	ENSP00000369664.3	A6NDW0
ZRSR2	ENST00000964213.1		c.23C>A	p.Thr8Lys	missense	Exon 1 of 11	ENSP00000634272.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1046911

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

339413

African (AFR)

AF:

0.00

AC:

AN:

24139

American (AMR)

AF:

0.00

AC:

AN:

25049

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18307

East Asian (EAS)

AF:

0.00

AC:

AN:

26775

South Asian (SAS)

AF:

0.00

AC:

AN:

49042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37705

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4045

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

817812

Other (OTH)

AF:

0.00

AC:

AN:

44037

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.1

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.013

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.61

M_CAP

Benign

0.0080

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.22

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.36

REVEL

Benign

0.0070

Sift

Benign

0.58

Sift4G

Benign

0.073

Polyphen

0.012

Vest4

0.089

MutPred

0.21

Loss of phosphorylation at T8 (P = 0.0099)

MVP

0.068

MPC

0.49

ClinPred

0.063

GERP RS

-1.6

PromoterAI

-0.57

Under-expression

(source)

Varity_R

0.042

gMVP

0.17

Mutation Taster

=98/2

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

Computational scores

Splicing

Publications

Other links and lift over