Variant X-15815730-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005089.4(ZRSR2):c.611G>A(p.Ser204Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000089 in 112,356 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Consequence

ZRSR2
NM_005089.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.48

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.384305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRSR2	NM_005089.4 linkuse as main transcript	c.611G>A	p.Ser204Asn	missense_variant	8/11	ENST00000307771.8	NP_005080.1	Q15696
ZRSR2	XM_011545589.4 linkuse as main transcript	c.680G>A	p.Ser227Asn	missense_variant	7/10		XP_011543891.3	A0A8I5KSD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZRSR2	ENST00000307771.8 linkuse as main transcript	c.611G>A	p.Ser204Asn	missense_variant	8/11	1	NM_005089.4	ENSP00000303015.7	Q15696
ZRSR2	ENST00000684799.1 linkuse as main transcript	c.533G>A	p.Ser178Asn	missense_variant	7/11			ENSP00000510773.1	A0A8I5KSD0
ZRSR2	ENST00000690252.1 linkuse as main transcript	n.611G>A		non_coding_transcript_exon_variant	8/13			ENSP00000510140.1	A0A8I5KRH1
ZRSR2	ENST00000691502.1 linkuse as main transcript	n.611G>A		non_coding_transcript_exon_variant	8/13			ENSP00000509336.1	A0A8I5QKS0

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34516

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000890

AC:

AN:

112356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34516

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2024

The c.611G>A (p.S204N) alteration is located in exon 8 (coding exon 8) of the ZRSR2 gene. This alteration results from a G to A substitution at nucleotide position 611, causing the serine (S) at amino acid position 204 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.041

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

M_CAP

Pathogenic

0.61

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.49

MutationAssessor

Benign

-0.96

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.10

REVEL

Uncertain

0.43

Sift

Benign

0.59

Sift4G

Benign

1.0

Polyphen

0.40

Vest4

0.48

MutPred

0.47

Loss of disorder (P = 0.0759);

MVP

0.73

MPC

0.45

ClinPred

0.79

GERP RS

5.4

Varity_R

0.32

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over