rs146593203

Variant names:

• chr15-50707809-G-C
• rs146593203
• NM_032802.4:c.1554C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-50707809-G-C
• chr15-50707809-G-A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_032802.4(SPPL2A):​c.1554C>G​(p.Val518Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,538,102 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (3 hom.)
• Consequence: SPPL2A NM_032802.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.104
• Publications: 0 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: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-50707809-G-C is Benign according to our data. Variant chr15-50707809-G-C is described in ClinVar as Benign. ClinVar VariationId is 1165397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.104 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPPL2A	NM_032802.4	MANE Select	c.1554C>G	p.Val518Val	synonymous	Exon 15 of 15	NP_116191.2
	SPPL2A	NM_001438111.1		c.1608C>G	p.Val536Val	synonymous	Exon 16 of 16	NP_001425040.1
	SPPL2A	NM_001438112.1		c.*34C>G		3_prime_UTR	Exon 14 of 14	NP_001425041.1	A0A8V8TLZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPPL2A	ENST00000261854.10	TSL:1 MANE Select	c.1554C>G	p.Val518Val	synonymous	Exon 15 of 15	ENSP00000261854.5	Q8TCT8
	SPPL2A	ENST00000951698.1		c.1611C>G	p.Val537Val	synonymous	Exon 16 of 16	ENSP00000621757.1
	SPPL2A	ENST00000951700.1		c.1515C>G	p.Val505Val	synonymous	Exon 16 of 16	ENSP00000621759.1

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 212 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00112 AC: 281 AN: 250926 AF XY: 0.00111

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.000435

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.00218

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00204 AC: 2823 AN: 1385868 Hom.: 3 Cov.: 23 AF XY: 0.00194 AC XY: 1347 AN XY: 693854

African (AFR) AF: 0.000468 AC: 15 AN: 32024

American (AMR) AF: 0.000337 AC: 15 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25696

East Asian (EAS) AF: 0.00 AC: 0 AN: 39318

South Asian (SAS) AF: 0.00 AC: 0 AN: 84596

European-Finnish (FIN) AF: 0.000319 AC: 17 AN: 53280

Middle Eastern (MID) AF: 0.000714 AC: 4 AN: 5602

European-Non Finnish (NFE) AF: 0.00260 AC: 2712 AN: 1042876

Other (OTH) AF: 0.00104 AC: 60 AN: 57910

GnomAD4 genome AF: 0.00139 AC: 212 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.00107 AC XY: 80 AN XY: 74426

African (AFR) AF: 0.000650 AC: 27 AN: 41542

American (AMR) AF: 0.000262 AC: 4 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00256 AC: 174 AN: 68024

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00203 Hom.: 0

Bravo AF: 0.00140

EpiCase AF: 0.00170

EpiControl AF: 0.00178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.40
DANN	Benign	0.55
PhyloP100		-0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs146593203; hg19: chr15-51000006;