rs9920753

Positions:

• chr15-50718881-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032802.4(SPPL2A):​c.1488+1059A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,876 control chromosomes in the GnomAD database, including 7,476 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 0.30 (7476 hom., cov: 31)
• Consequence: SPPL2A NM_032802.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

Genes affected

SPPL2A (HGNC:30227): (signal peptide peptidase like 2A) This gene encodes a member of the GXGD family of aspartic proteases, which are transmembrane proteins with two conserved catalytic motifs localized within the membrane-spanning regions, as well as a member of the signal peptide peptidase-like protease (SPPL) family. This protein is expressed in all major adult human tissues and localizes to late endosomal compartments and lysosomal membranes. A pseudogene of this gene also lies on chromosome 15. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPPL2A	NM_032802.4	c.1488+1059A>T		intron_variant		ENST00000261854.10	NP_116191.2
SPPL2A	XM_005254722.4	c.1542+1059A>T		intron_variant			XP_005254779.1
SPPL2A	XM_017022680.2	c.1381+3243A>T		intron_variant			XP_016878169.1
SPPL2A	XM_017022681.2	c.1327+3243A>T		intron_variant			XP_016878170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPPL2A	ENST00000261854.10	c.1488+1059A>T		intron_variant		1	NM_032802.4	ENSP00000261854	P1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45822 AN: 151756 Hom.: 7471 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.329

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.302 AC: 45857 AN: 151876 Hom.: 7476 Cov.: 31 AF XY: 0.305 AC XY: 22614 AN XY: 74208

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.329

Alfa AF: 0.323 Hom.: 1021

Bravo AF: 0.291

Asia WGS AF: 0.431 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.38

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

Other links and lift over

dbSNP: rs9920753; hg19: chr15-51011078;