rs1555447569

Positions:

• chr15-76471313-CATTG-C

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_020843.4(SCAPER):​c.2973_2976delCAAT​(p.Ile991fs) 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SCAPER NM_020843.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 2.50

Genes affected

SCAPER (HGNC:13081): (S-phase cyclin A associated protein in the ER) Predicted to enable nucleic acid binding activity and zinc ion binding activity. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-76471313-CATTG-C is Pathogenic according to our data. Variant chr15-76471313-CATTG-C is described in ClinVar as [Pathogenic]. Clinvar id is 417685.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAPER	NM_020843.4	c.2973_2976delCAAT	p.Ile991fs	frameshift_variant	25/32	ENST00000563290.6	NP_065894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAPER	ENST00000563290.6	c.2973_2976delCAAT	p.Ile991fs	frameshift_variant	25/32	5	NM_020843.4	ENSP00000454973.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, moderate;C1263846:Attention deficit hyperactivity disorder;C4551714:Rod-cone dystrophy Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Department of Genetics, Fundacion Jimenez Diaz University Hospital

Jan 01, 2017

- -

Intellectual developmental disorder and retinitis pigmentosa; IDDRP Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs1555447569; hg19: chr15-76763654;