rs9920753

Variant names:

• chr15-50718881-T-A
• rs9920753
• NM_032802.4:c.1488+1059A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

SPPL2A Gene-Disease associations (from GenCC):

• immunodeficiency 86

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032802.4. 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
	SPPL2A	NM_032802.4	MANE Select	c.1488+1059A>T		intron	N/A	NP_116191.2
	SPPL2A	NM_001438111.1		c.1542+1059A>T		intron	N/A	NP_001425040.1
	SPPL2A	NM_001438112.1		c.1327+3243A>T		intron	N/A	NP_001425041.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPPL2A	ENST00000261854.10	TSL:1 MANE Select	c.1488+1059A>T		intron	N/A	ENSP00000261854.5
	SPPL2A	ENST00000698136.1		n.2565A>T		non_coding_transcript_exon	Exon 12 of 12
	SPPL2A	ENST00000698137.1		n.2722A>T		non_coding_transcript_exon	Exon 14 of 14

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

African (AFR) AF: 0.177 AC: 7353 AN: 41434

American (AMR) AF: 0.282 AC: 4295 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 953 AN: 3472

East Asian (EAS) AF: 0.570 AC: 2928 AN: 5138

South Asian (SAS) AF: 0.327 AC: 1575 AN: 4816

European-Finnish (FIN) AF: 0.340 AC: 3569 AN: 10506

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 24001 AN: 67974

Other (OTH) AF: 0.329 AC: 694 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.38
PhyloP100		-0.17
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: rs9920753; hg19: chr15-51011078;