rs1305542291

Variant names:

• chr15-76381427-C-G
• rs1305542291
• NM_020843.4:c.3656G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-76381427-C-G
• chr15-76381427-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PM5 BP4

The NM_020843.4(SCAPER):​c.3656G>C​(p.Ser1219Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1219N) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SCAPER NM_020843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.52
• 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. 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr15-76381427-C-T is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 427855.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.28794557).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAPER	NM_020843.4	MANE Select	c.3656G>C	p.Ser1219Thr	missense	Exon 28 of 32	NP_065894.2
	SCAPER	NM_001353009.2		c.3674G>C	p.Ser1225Thr	missense	Exon 29 of 33	NP_001339938.1
	SCAPER	NM_001353011.2		c.3272G>C	p.Ser1091Thr	missense	Exon 29 of 33	NP_001339940.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAPER	ENST00000563290.6	TSL:5 MANE Select	c.3656G>C	p.Ser1219Thr	missense	Exon 28 of 32	ENSP00000454973.1
	SCAPER	ENST00000324767.11	TSL:1	c.3656G>C	p.Ser1219Thr	missense	Exon 27 of 31	ENSP00000326924.7
	SCAPER	ENST00000538941.6	TSL:1	c.2918G>C	p.Ser973Thr	missense	Exon 28 of 32	ENSP00000442190.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461568 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727052

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111830

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.0048	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.10
Sift	Benign	0.44	T
Sift4G	Benign	0.079	T
Vest4		0.47
MVP		0.45
MPC		0.83
ClinPred		0.71	D
GERP RS		5.8
Varity_R		0.21
gMVP		0.41
Mutation Taster		=56/44	polymorphism

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: rs1305542291; hg19: chr15-76673768;