NM_020843.4:c.3818_3819delGTinsTC

Variant names:

• chr15-76376198-AC-GA
• NM_020843.4:c.3818_3819delGTinsTC
• SCAPER p.Cys1273Phe

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_020843.4(SCAPER):c.3818_3819delGTinsTC (p.Cys1273Phe) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 7.51). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.C1273Y: Uncertain_significance (ClinVar VariationId 2268550, 1 star)

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCAPER NM_020843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.51
• Publications: 0 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. Acts upstream of or within retina development in camera-type eye. Located in nuclear speck. [provided by Alliance of Genome Resources, Jun 2026]

SCAPER Gene-Disease associations (from GenCC):

• intellectual developmental disorder and retinitis pigmentosa; IDDRP

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

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD+AR) (threshold 0.0001) — PM2 moderate.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	SCAPER NM_020843.4	MANE Select	c.3818_3819delGTinsTC p.Cys1273Phe	missense	N/A	Prot: NP_065894.2 UniProt:
	SCAPER NM_001353009.2		c.3836_3837delGTinsTC p.Cys1279Phe	missense	N/A	Prot: NP_001339938.1
	SCAPER NM_001353011.2		c.3434_3435delGTinsTC p.Cys1145Phe	missense	N/A	Prot: NP_001339940.1

SCAPER NM_020843.4

MANE Select

HGVSc / HGVSpc.3818_3819delGTinsTCp.Cys1273Phe

Exon rankN/A

missense

Prot: NP_065894.2UniProt: Q9BY12-1

SCAPER NM_001353009.2

HGVSc / HGVSpc.3836_3837delGTinsTCp.Cys1279Phe

Exon rankN/A

missense

Prot: NP_001339938.1

SCAPER NM_001353011.2

HGVSc / HGVSpc.3434_3435delGTinsTCp.Cys1145Phe

Exon rankN/A

missense

Prot: NP_001339940.1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	SCAPER ENST00000563290.6	TSL:5MANE Select	c.3818_3819delGTinsTC p.Cys1273Phe	missense	N/A	Prot: ENSP00000454973.1 UniProt:
	SCAPER ENST00000324767.11	TSL:1	c.3818_3819delGTinsTC p.Cys1273Phe	missense	N/A	Prot: ENSP00000326924.7 UniProt:
	SCAPER ENST00000538941.6	TSL:1	c.3080_3081delGTinsTC p.Cys1027Phe	missense	N/A	Prot: ENSP00000442190.2 UniProt:

SCAPER ENST00000563290.6

TSL:5MANE Select

HGVSc / HGVSpc.3818_3819delGTinsTCp.Cys1273Phe

Exon rankN/A

missense

Prot: ENSP00000454973.1UniProt: Q9BY12-1

SCAPER ENST00000324767.11

TSL:1

HGVSc / HGVSpc.3818_3819delGTinsTCp.Cys1273Phe

Exon rankN/A

missense

Prot: ENSP00000326924.7UniProt: Q9BY12-1

SCAPER ENST00000538941.6

TSL:1

HGVSc / HGVSpc.3080_3081delGTinsTCp.Cys1027Phe

Exon rankN/A

missense

Prot: ENSP00000442190.2UniProt: Q9BY12-3

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Uncertain	7.5

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr15-76668539;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar