rs1555447569

Variant names:

• chr15-76471313-CATTG-C
• rs1555447569
• NM_020843.4:c.2973_2976delCAAT

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_020843.4(SCAPER):​c.2973_2976delCAAT​(p.Ile991MetfsTer26) 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 (★). Synonymous variant affecting the same amino acid position (i.e. I991I) has been classified as Likely benign. 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
• Publications: 1 publications found

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]

SCAPER Gene-Disease associations (from GenCC):

• intellectual developmental disorder and retinitis pigmentosa; IDDRP

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 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 rank	MANE	Protein	UniProt
SCAPER	NM_020843.4	c.2973_2976delCAAT	p.Ile991MetfsTer26	frameshift_variant	Exon 25 of 32	ENST00000563290.6	NP_065894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAPER	ENST00000563290.6	c.2973_2976delCAAT	p.Ile991MetfsTer26	frameshift_variant	Exon 25 of 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

Jan 01, 2017

Department of Genetics, Fundacion Jimenez Diaz University Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

- -

Intellectual developmental disorder and retinitis pigmentosa; IDDRP Pathogenic:1

Nov 20, 2018

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=14/186	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1555447569; hg19: chr15-76763654;