chrX-15822912-C-CTA

Position:

• chrX-15822912-C-CTA

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_005089.4(ZRSR2):​c.1120_1121dupTA​(p.Ser375fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: ZRSR2 NM_005089.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.833

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.226 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-15822912-C-CTA is Pathogenic according to our data. Variant chrX-15822912-C-CTA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3341118.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRSR2	NM_005089.4	c.1120_1121dupTA	p.Ser375fs	frameshift_variant	11/11	ENST00000307771.8	NP_005080.1
ZRSR2	XM_011545589.4	c.1189_1190dupTA	p.Ser398fs	frameshift_variant	10/10		XP_011543891.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRSR2	ENST00000307771.8	c.1120_1121dupTA	p.Ser375fs	frameshift_variant	11/11	1	NM_005089.4	ENSP00000303015.7
ZRSR2	ENST00000684799.1	c.1042_1043dupTA	p.Ser349fs	frameshift_variant	10/11			ENSP00000510773.1
ZRSR2	ENST00000690252.1	n.1120_1121dupTA		non_coding_transcript_exon_variant	11/13			ENSP00000510140.1
ZRSR2	ENST00000691502.1	n.1006_1007dupTA		non_coding_transcript_exon_variant	11/13			ENSP00000509336.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Centre for Clinical Genetics and Genomic Diagnostics, Zealand University Hospital

Nov 10, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-15841035;