15-76404427-T-C

Variant names:

• chr15-76404427-T-C
• rs3743175
• NM_020843.4:c.3467+97A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020843.4(SCAPER):​c.3467+97A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 1,209,514 control chromosomes in the GnomAD database, including 3,055 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.078 (525 hom., cov: 31)
  • Exomes 𝑓: 0.065 (2530 hom.)
• Consequence: SCAPER NM_020843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAPER	NM_020843.4	c.3467+97A>G		intron_variant	Intron 27 of 31	ENST00000563290.6	NP_065894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAPER	ENST00000563290.6	c.3467+97A>G		intron_variant	Intron 27 of 31	5	NM_020843.4	ENSP00000454973.1
SCAPER	ENST00000324767.11	c.3467+97A>G		intron_variant	Intron 26 of 30	1		ENSP00000326924.7
SCAPER	ENST00000538941.6	c.2729+97A>G		intron_variant	Intron 27 of 31	1		ENSP00000442190.2
SCAPER	ENST00000303521.10	n.3531+97A>G		intron_variant	Intron 26 of 26	2

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11821 AN: 152112 Hom.: 525 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0726

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0351

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.0616

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0775

GnomAD4 exome AF: 0.0651 AC: 68817 AN: 1057284 Hom.: 2530 AF XY: 0.0653 AC XY: 34122 AN XY: 522250

African (AFR) AF: 0.102 AC: 2459 AN: 24082

American (AMR) AF: 0.0444 AC: 1148 AN: 25854

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 2086 AN: 16884

East Asian (EAS) AF: 0.0241 AC: 830 AN: 34416

South Asian (SAS) AF: 0.0550 AC: 2623 AN: 47682

European-Finnish (FIN) AF: 0.0560 AC: 1914 AN: 34174

Middle Eastern (MID) AF: 0.101 AC: 464 AN: 4578

European-Non Finnish (NFE) AF: 0.0656 AC: 54068 AN: 824568

Other (OTH) AF: 0.0716 AC: 3225 AN: 45046

GnomAD4 genome AF: 0.0777 AC: 11830 AN: 152230 Hom.: 525 Cov.: 31 AF XY: 0.0782 AC XY: 5820 AN XY: 74442

African (AFR) AF: 0.106 AC: 4411 AN: 41518

American (AMR) AF: 0.0725 AC: 1110 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3468

East Asian (EAS) AF: 0.0352 AC: 182 AN: 5174

South Asian (SAS) AF: 0.0574 AC: 277 AN: 4824

European-Finnish (FIN) AF: 0.0616 AC: 654 AN: 10614

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0671 AC: 4563 AN: 68014

Other (OTH) AF: 0.0772 AC: 163 AN: 2112

Alfa AF: 0.0720 Hom.: 816

Bravo AF: 0.0794

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.79
DANN	Benign	0.88
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs3743175; hg19: chr15-76696768; COSMIC: COSV57739279;