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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• 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 VariationId is 417685.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020843.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAPER	NM_020843.4	MANE Select	c.2973_2976delCAAT	p.Ile991MetfsTer26	frameshift	Exon 25 of 32	NP_065894.2	Q9BY12-1
	SCAPER	NM_001353009.2		c.2991_2994delCAAT	p.Ile997MetfsTer26	frameshift	Exon 26 of 33	NP_001339938.1
	SCAPER	NM_001353011.2		c.2589_2592delCAAT	p.Ile863MetfsTer26	frameshift	Exon 26 of 33	NP_001339940.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAPER	ENST00000563290.6	TSL:5 MANE Select	c.2973_2976delCAAT	p.Ile991MetfsTer26	frameshift	Exon 25 of 32	ENSP00000454973.1	Q9BY12-1
	SCAPER	ENST00000324767.11	TSL:1	c.2973_2976delCAAT	p.Ile991MetfsTer26	frameshift	Exon 24 of 31	ENSP00000326924.7	Q9BY12-1
	SCAPER	ENST00000538941.6	TSL:1	c.2235_2238delCAAT	p.Ile745MetfsTer26	frameshift	Exon 25 of 32	ENSP00000442190.2	Q9BY12-3

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

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Intellectual developmental disorder and retinitis pigmentosa; IDDRP (1)
1	-	-	Moderate intellectual disability;C1263846:Attention deficit hyperactivity disorder;C4551714:Rod-cone dystrophy (1)

Computational scores

Source: dbNSFP v4.9

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;