Variant X-15822994-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005089.4(ZRSR2):c.1201C>T(p.Arg401Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,210,808 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 71 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.00012 ( 0 hom. 67 hem. )

Consequence

ZRSR2
NM_005089.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.511

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057428777).

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.1201C>T	p.Arg401Cys	missense_variant	11/11	ENST00000307771.8
ZRSR2	XM_011545589.4 linkuse as main transcript	c.1270C>T	p.Arg424Cys	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZRSR2	ENST00000307771.8 linkuse as main transcript	c.1201C>T	p.Arg401Cys	missense_variant	11/11	1	NM_005089.4	P2
ZRSR2	ENST00000684799.1 linkuse as main transcript	c.1123C>T	p.Arg375Cys	missense_variant	10/11			A2
ZRSR2	ENST00000690252.1 linkuse as main transcript	c.1201C>T	p.Arg401Cys	missense_variant, NMD_transcript_variant	11/13
ZRSR2	ENST00000691502.1 linkuse as main transcript	c.1087C>T	p.Arg363Cys	missense_variant, NMD_transcript_variant	11/13

Frequencies

GnomAD3 genomes

AF:

0.0000800

AC:

AN:

112569

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34729

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00188

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000730

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000284

AC:

AN:

183146

Hom.:

AF XY:

0.000486

AC XY:

AN XY:

67842

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000490

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000121

AC:

133

AN:

1098239

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

AN XY:

363595

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00279

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000831

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000309

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.0000800

AC:

AN:

112569

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34729

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00188

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000730

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000375

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000608

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.0000545

EpiControl

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, 2021

The c.1201C>T (p.R401C) alteration is located in exon 11 (coding exon 11) of the ZRSR2 gene. This alteration results from a C to T substitution at nucleotide position 1201, causing the arginine (R) at amino acid position 401 to be replaced by a cysteine (C). 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

0.079

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.81

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.034

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.43

M_CAP

Benign

0.015

MetaRNN

Benign

0.0057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.9

REVEL

Benign

0.069

Sift

Benign

0.055

Sift4G

Uncertain

0.0080

Polyphen

0.70

Vest4

0.050

MutPred

0.27

Loss of solvent accessibility (P = 0.0199);

MVP

0.043

MPC

0.56

ClinPred

0.057

GERP RS

2.9

Varity_R

0.10

gMVP

0.42

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

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