Variant chrX-15808251-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_005089.4(ZRSR2):c.418C>T(p.Leu140Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,203,220 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000043 ( 0 hom. 11 hem. )

Consequence

ZRSR2
NM_005089.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.44

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant X-15808251-C-T is Benign according to our data. Variant chrX-15808251-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660059.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.43 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRSR2	NM_005089.4 linkuse as main transcript	c.418C>T	p.Leu140Leu	synonymous_variant	6/11	ENST00000307771.8	NP_005080.1	Q15696
ZRSR2	XM_011545589.4 linkuse as main transcript	c.487C>T	p.Leu163Leu	synonymous_variant	5/10		XP_011543891.3	A0A8I5KSD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZRSR2	ENST00000307771.8 linkuse as main transcript	c.418C>T	p.Leu140Leu	synonymous_variant	6/11	1	NM_005089.4	ENSP00000303015.7	Q15696
ZRSR2	ENST00000684799.1 linkuse as main transcript	c.340C>T	p.Leu114Leu	synonymous_variant	5/11			ENSP00000510773.1	A0A8I5KSD0
ZRSR2	ENST00000690252.1 linkuse as main transcript	n.418C>T		non_coding_transcript_exon_variant	6/13			ENSP00000510140.1	A0A8I5KRH1
ZRSR2	ENST00000691502.1 linkuse as main transcript	n.418C>T		non_coding_transcript_exon_variant	6/13			ENSP00000509336.1	A0A8I5QKS0

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

112046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34218

show subpopulations

Gnomad AFR

AF:

0.0000324

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000170

AC:

AN:

176847

Hom.:

AF XY:

0.0000161

AC XY:

AN XY:

61983

show subpopulations

Gnomad AFR exome

AF:

0.0000772

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000582

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000431

AC:

AN:

1091174

Hom.:

Cov.:

AF XY:

0.0000308

AC XY:

AN XY:

357152

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:

0.000170

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000393

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.0000268

AC:

AN:

112046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34218

show subpopulations

Gnomad4 AFR

AF:

0.0000324

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:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

ZRSR2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

9.8

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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