Genetic Variant NM_020843.4:c.2973_2976delCAAT (chr15-76471313-CATTG-C) – ACMG Classification: Pathogenic (12 pts)

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_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

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 2.50

Publications

1 publications found

Variant links:

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

SCAPER links:

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ACMG classification

Classification was made for transcript

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

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

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.:

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

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Intellectual developmental disorder and retinitis pigmentosa; IDDRP (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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over