NM_001085382.2:c.1550C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001085382.2(PSAPL1):c.1550C>T(p.Ala517Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000789 in 1,420,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

PSAPL1
NM_001085382.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.482

Publications

0 publications found

Variant links:

Genes affected

PSAPL1 (HGNC:33131): (prosaposin like 1) This gene encodes a protein that is related to the glycoprotein prosaposin. Based on sequence similarity between the encoded protein and prosaposin, it is predicted that the encoded protein is a preproprotein that is proteolytically processed to generate multiple protein products. These predicted products include saposins A-like, B-like, C-like, and D-like, which may play a role in the lysosomal degradation of sphingolipids. [provided by RefSeq, Jul 2015]

PSAPL1 links:

SORCS2 (HGNC:16698): (sortilin related VPS10 domain containing receptor 2) This gene encodes one family member of vacuolar protein sorting 10 (VPS10) domain-containing receptor proteins. The VPS10 domain name comes from the yeast carboxypeptidase Y sorting receptor Vps10 protein. Members of this gene family are large with many exons but the CDS lengths are usually less than 3700 nt. Very large introns typically separate the exons encoding the VPS10 domain; the remaining exons are separated by much smaller-sized introns. These genes are strongly expressed in the central nervous system. [provided by RefSeq, Jul 2008]

SORCS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008903712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSAPL1	NM_001085382.2 link	c.1550C>T	p.Ala517Val	missense_variant	Exon 1 of 1	ENST00000319098.7	NP_001078851.1	Q6NUJ1
SORCS2	NM_020777.3 link	c.548+36975G>A		intron_variant	Intron 2 of 26	ENST00000507866.6	NP_065828.2	Q96PQ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PSAPL1	ENST00000319098.7 link	c.1550C>T	p.Ala517Val	missense_variant	Exon 1 of 1	6	NM_001085382.2	ENSP00000317445.4	Q6NUJ1
SORCS2	ENST00000507866.6 link	c.548+36975G>A		intron_variant	Intron 2 of 26	1	NM_020777.3	ENSP00000422185.2	Q96PQ0
SORCS2	ENST00000511199.1 link	n.163+36975G>A		intron_variant	Intron 2 of 5	4

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000140

AC:

AN:

71410

AF XY:

0.0000287

show subpopulations

Gnomad AFR exome

AF:

0.00120

Gnomad AMR exome

AF:

0.000139

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000318

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1267672

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

610788

show subpopulations

African (AFR)

AF:

0.00145

AC:

AN:

27670

American (AMR)

AF:

0.0000624

AC:

AN:

16034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18292

East Asian (EAS)

AF:

0.00

AC:

AN:

33068

South Asian (SAS)

AF:

0.00

AC:

AN:

55238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44648

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5134

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1015350

Other (OTH)

AF:

0.0000957

AC:

AN:

52238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000433

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00156

AC:

AN:

41594

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000428

Hom.:

Bravo

AF:

0.000502

ESP6500AA

AF:

0.00217

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000790

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1550C>T (p.A517V) alteration is located in exon 1 (coding exon 1) of the PSAPL1 gene. This alteration results from a C to T substitution at nucleotide position 1550, causing the alanine (A) at amino acid position 517 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.2

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.00061

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0093

LIST_S2

Benign

0.36

M_CAP

Benign

0.0046

MetaRNN

Benign

0.0089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.14

PhyloP100

-0.48

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.30

REVEL

Benign

0.040

Sift

Benign

0.060

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.029

MVP

0.33

MPC

0.026

ClinPred

0.0065

GERP RS

-5.3

Varity_R

0.027

gMVP

0.29

Mutation Taster

=99/1

polymorphism

(source)

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

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NM_001085382.2:c.1550C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over