10-71819648-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002778.4(PSAP):c.1193-26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,892 control chromosomes in the GnomAD database, including 29,058 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2225 hom., cov: 32)

Exomes 𝑓: 0.19 ( 26833 hom. )

Consequence

PSAP
NM_002778.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.62

Variant links:

Genes affected

PSAP (HGNC:9498): (prosaposin) This gene encodes a highly conserved preproprotein that is proteolytically processed to generate four main cleavage products including saposins A, B, C, and D. Each domain of the precursor protein is approximately 80 amino acid residues long with nearly identical placement of cysteine residues and glycosylation sites. Saposins A-D localize primarily to the lysosomal compartment where they facilitate the catabolism of glycosphingolipids with short oligosaccharide groups. The precursor protein exists both as a secretory protein and as an integral membrane protein and has neurotrophic activities. Mutations in this gene have been associated with Gaucher disease and metachromatic leukodystrophy. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

PSAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-71819648-C-T is Benign according to our data. Variant chr10-71819648-C-T is described in ClinVar as [Benign]. Clinvar id is 258808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
PSAP	NM_002778.4 linkuse as main transcript	c.1193-26G>A	intron_variant	ENST00000394936.8
PSAP	NM_001042465.3 linkuse as main transcript	c.1202-26G>A	intron_variant
PSAP	NM_001042466.3 linkuse as main transcript	c.1199-26G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSAP	ENST00000394936.8 linkuse as main transcript	c.1193-26G>A		intron_variant		1	NM_002778.4	P1	P07602-1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25442

AN:

152032

Hom.:

2225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.169

GnomAD3 exomes

AF:

0.174

AC:

43711

AN:

250966

Hom.:

4057

AF XY:

0.173

AC XY:

23475

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.120

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.237

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.222

Gnomad NFE exome

AF:

0.192

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.189

AC:

275872

AN:

1461740

Hom.:

26833

Cov.:

AF XY:

0.186

AC XY:

135561

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.275

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.221

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.182

GnomAD4 genome

AF:

0.167

AC:

25446

AN:

152152

Hom.:

2225

Cov.:

AF XY:

0.168

AC XY:

12520

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.171

Gnomad4 EAS

AF:

0.248

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.225

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.109

Hom.:

247

Bravo

AF:

0.160

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Combined PSAP deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

not provided

Benign:1

Benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Oct 22, 2015

- -

Krabbe disease due to saposin A deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Sphingolipid activator protein 1 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

Cadd

Benign

0.016

Dann

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over