NM_020843.4:c.3818G>A

Variant names:

• chr15-76376199-C-T
• rs1567020043
• NM_020843.4:c.3818G>A
• SCAPER p.Cys1273Tyr

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.3818G>A (p.Cys1273Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 7.51). Variant has been reported in ClinVar as Uncertain Significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCAPER NM_020843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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.3818G>A p.Cys1273Tyr	missense	Exon 29 of 32	Prot: NP_065894.2 UniProt:
	SCAPER NM_001353009.2		c.3836G>A p.Cys1279Tyr	missense	Exon 30 of 33	Prot: NP_001339938.1
	SCAPER NM_001353011.2		c.3434G>A p.Cys1145Tyr	missense	Exon 30 of 33	Prot: NP_001339940.1

SCAPER NM_020843.4

MANE Select

HGVSc / HGVSpc.3818G>Ap.Cys1273Tyr

Exon rankExon 29 of 32

missense

Prot: NP_065894.2UniProt: Q9BY12-1

SCAPER NM_001353009.2

HGVSc / HGVSpc.3836G>Ap.Cys1279Tyr

Exon rankExon 30 of 33

missense

Prot: NP_001339938.1

SCAPER NM_001353011.2

HGVSc / HGVSpc.3434G>Ap.Cys1145Tyr

Exon rankExon 30 of 33

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.3818G>A p.Cys1273Tyr	missense	Exon 29 of 32	Prot: ENSP00000454973.1 UniProt:
	SCAPER ENST00000324767.11	TSL:1	c.3818G>A p.Cys1273Tyr	missense	Exon 28 of 31	Prot: ENSP00000326924.7 UniProt:
	SCAPER ENST00000538941.6	TSL:1	c.3080G>A p.Cys1027Tyr	missense	Exon 29 of 32	Prot: ENSP00000442190.2 UniProt:

SCAPER ENST00000563290.6

TSL:5MANE Select

HGVSc / HGVSpc.3818G>Ap.Cys1273Tyr

Exon rankExon 29 of 32

missense

Prot: ENSP00000454973.1UniProt: Q9BY12-1

SCAPER ENST00000324767.11

TSL:1

HGVSc / HGVSpc.3818G>Ap.Cys1273Tyr

Exon rankExon 28 of 31

missense

Prot: ENSP00000326924.7UniProt: Q9BY12-1

SCAPER ENST00000538941.6

TSL:1

HGVSc / HGVSpc.3080G>Ap.Cys1027Tyr

Exon rankExon 29 of 32

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 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:30
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 3 sources

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Pathogenic	32
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
FuncVEP CTI	Pathogenic	0.90
GPN-Star LLR	N/A	-8.2
GPN-Star score	N/A	8.2
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.7	M
PhyloP100	Uncertain	7.5
popEVE	Benign	-4.0
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.014	D
Varity_R	N/A	0.60
VESM-3B	Benign	-12

Showing 27 of 27 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

dbSNP: rs1567020043;

hg19: chr15-76668540;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar