Variant X-15822802-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005089.4(ZRSR2):c.1009A>G(p.Asn337Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,211,076 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 54 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.00013 ( 0 hom. 50 hem. )

Consequence

ZRSR2
NM_005089.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.02

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZRSR2	NM_005089.4 linkuse as main transcript	c.1009A>G	p.Asn337Asp	missense_variant	11/11	ENST00000307771.8
ZRSR2	XM_011545589.4 linkuse as main transcript	c.1078A>G	p.Asn360Asp	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZRSR2	ENST00000307771.8 linkuse as main transcript	c.1009A>G	p.Asn337Asp	missense_variant	11/11	1	NM_005089.4	P2
ZRSR2	ENST00000684799.1 linkuse as main transcript	c.931A>G	p.Asn311Asp	missense_variant	10/11			A2
ZRSR2	ENST00000690252.1 linkuse as main transcript	c.1009A>G	p.Asn337Asp	missense_variant, NMD_transcript_variant	11/13
ZRSR2	ENST00000691502.1 linkuse as main transcript	c.938-43A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000124

AC:

AN:

112807

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

34943

show subpopulations

Gnomad AFR

AF:

0.000129

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:

0.000187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000381

AC:

AN:

183520

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

67946

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000732

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000135

AC:

148

AN:

1098269

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

AN XY:

363623

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000172

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.000124

AC:

AN:

112807

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

34943

show subpopulations

Gnomad4 AFR

AF:

0.000129

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:

0.000187

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Mar 25, 2022

The c.1009A>G (p.N337D) alteration is located in exon 11 (coding exon 11) of the ZRSR2 gene. This alteration results from a A to G substitution at nucleotide position 1009, causing the asparagine (N) at amino acid position 337 to be replaced by an aspartic acid (D). 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

-0.18

BayesDel_noAF

Benign

-0.31

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.069

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.19

Sift

Benign

0.16

Sift4G

Benign

0.33

Polyphen

0.60

Vest4

0.70

MVP

0.57

MPC

0.69

ClinPred

0.24

GERP RS

5.5

Varity_R

0.67

gMVP

0.68

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