Genetic Variant SCAPER:p.Ser1309Ile (chr15-76354070-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020843.4(SCAPER):c.3926G>T(p.Ser1309Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,610,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

SCAPER
NM_020843.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.46

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.863

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAPER	NM_020843.4 link	c.3926G>T	p.Ser1309Ile	missense_variant	Exon 30 of 32	ENST00000563290.6	NP_065894.2	Q9BY12-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAPER	ENST00000563290.6 link	c.3926G>T	p.Ser1309Ile	missense_variant	Exon 30 of 32	5	NM_020843.4	ENSP00000454973.1		Q9BY12-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000244

AC:

AN:

245498

Hom.:

AF XY:

0.0000300

AC XY:

AN XY:

133478

show subpopulations

Gnomad AFR exome

AF:

0.0000657

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000447

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000480

AC:

AN:

1458742

Hom.:

Cov.:

AF XY:

0.0000524

AC XY:

AN XY:

725794

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000612

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000900

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SCAPER-related disorder

Uncertain:1

Aug 23, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The SCAPER c.3944G>T variant is predicted to result in the amino acid substitution p.Ser1315Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0066% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;T

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

.;D;D

M_CAP

Benign

0.030

MetaRNN

Pathogenic

0.86

D;D;D

MetaSVM

Benign

-0.43

MutationAssessor

Pathogenic

3.1

M;.;M

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-4.8

D;D;D

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Vest4

0.89

MVP

0.75

MPC

1.1

ClinPred

0.99

GERP RS

5.8

Varity_R

0.86

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over