NM_020843.4:c.3818G>T

Variant names:

• chr15-76376199-C-A
• rs1567020043
• NM_020843.4:c.3818G>T
• 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.3818G>T (p.Cys1273Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a cumulative frequency of 0.000000684 (AC=1) in the gnomAD database across 1,461,678 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.000000684. 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). 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• 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		Very rare in gnomAD for AD/XL gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.000000684 — very rare for AD+AR gene (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>T p.Cys1273Phe	missense	Exon 29 of 32	Prot: NP_065894.2 UniProt:
	SCAPER NM_001353009.2		c.3836G>T p.Cys1279Phe	missense	Exon 30 of 33	Prot: NP_001339938.1
	SCAPER NM_001353011.2		c.3434G>T p.Cys1145Phe	missense	Exon 30 of 33	Prot: NP_001339940.1

SCAPER NM_020843.4

MANE Select

HGVSc / HGVSpc.3818G>Tp.Cys1273Phe

Exon rankExon 29 of 32

missense

Prot: NP_065894.2UniProt: Q9BY12-1

SCAPER NM_001353009.2

HGVSc / HGVSpc.3836G>Tp.Cys1279Phe

Exon rankExon 30 of 33

missense

Prot: NP_001339938.1

SCAPER NM_001353011.2

HGVSc / HGVSpc.3434G>Tp.Cys1145Phe

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>T p.Cys1273Phe	missense	Exon 29 of 32	Prot: ENSP00000454973.1 UniProt:
	SCAPER ENST00000324767.11	TSL:1	c.3818G>T p.Cys1273Phe	missense	Exon 28 of 31	Prot: ENSP00000326924.7 UniProt:
	SCAPER ENST00000538941.6	TSL:1	c.3080G>T p.Cys1027Phe	missense	Exon 29 of 32	Prot: ENSP00000442190.2 UniProt:

SCAPER ENST00000563290.6

TSL:5MANE Select

HGVSc / HGVSpc.3818G>Tp.Cys1273Phe

Exon rankExon 29 of 32

missense

Prot: ENSP00000454973.1UniProt: Q9BY12-1

SCAPER ENST00000324767.11

TSL:1

HGVSc / HGVSpc.3818G>Tp.Cys1273Phe

Exon rankExon 28 of 31

missense

Prot: ENSP00000326924.7UniProt: Q9BY12-1

SCAPER ENST00000538941.6

TSL:1

HGVSc / HGVSpc.3080G>Tp.Cys1027Phe

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 4 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD2 exomes	AF: 0.00000401	AC:1	Hom:	AN:249084	Cov:
GnomAD4 exome	AF: 6.84e-7	AC:1	Hom:0	AN:1461678	Cov:30
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 4 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Pathogenic	27
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	1.0	D
FuncVEP CTI	Pathogenic	0.85
GPN-Star LLR	N/A	-9.0
GPN-Star score	N/A	9.0
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100	Uncertain	7.5
popEVE	Benign	-3.7
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.38
Sift	Benign	0.040	D
Sift4G	Benign	0.078	T
Varity_R	N/A	0.60
VESM-3B	Benign	-10

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