chr10-71819460-C-T

Variant names:

Variant summary

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

The NM_002778.4(PSAP):c.1350+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,782 control chromosomes in the GnomAD database, including 29,039 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2223 hom., cov: 33)

Exomes 𝑓: 0.19 ( 26816 hom. )

Consequence

PSAP
NM_002778.4 splice_region, intron

Scores

Splicing: ADA: 0.5971

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:18

Conservation

PhyloP100: 0.130

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=-0.78).

BP6

Variant 10-71819460-C-T is Benign according to our data. Variant chr10-71819460-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258809.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	Exon rank	MANE	Protein	UniProt
PSAP	NM_002778.4 link	c.1350+5G>A	splice_region_variant, intron_variant	Intron 11 of 13	ENST00000394936.8	NP_002769.1	P07602-1A0A024QZQ2
PSAP	NM_001042465.3 link	c.1359+5G>A	splice_region_variant, intron_variant	Intron 12 of 14		NP_001035930.1	P07602-3
PSAP	NM_001042466.3 link	c.1356+5G>A	splice_region_variant, intron_variant	Intron 12 of 14		NP_001035931.1	P07602-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSAP	ENST00000394936.8 link	c.1350+5G>A		splice_region_variant, intron_variant	Intron 11 of 13	1	NM_002778.4	ENSP00000378394.3		P07602-1
PSAP	ENST00000495196.1 link	n.-189G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25436

AN:

152134

Hom.:

2223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.168

GnomAD3 exomes

AF:

0.174

AC:

43735

AN:

251246

Hom.:

4064

AF XY:

0.173

AC XY:

23497

AN XY:

135832

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:

275761

AN:

1461528

Hom.:

26816

Cov.:

AF XY:

0.186

AC XY:

135527

AN XY:

727092

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:

0.129

Gnomad4 FIN exome

AF:

0.221

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.181

GnomAD4 genome

AF:

0.167

AC:

25437

AN:

152254

Hom.:

2223

Cov.:

AF XY:

0.168

AC XY:

12514

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.123

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:

0.166

Alfa

AF:

0.180

Hom.:

3290

Bravo

AF:

0.160

Asia WGS

AF:

0.138

AC:

481

AN:

3478

EpiCase

AF:

0.179

EpiControl

AF:

0.183

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:18

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 22, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sphingolipid activator protein 1 deficiency

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Combined PSAP deficiency

Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Krabbe disease due to saposin A deficiency

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Metachromatic leukodystrophy

Benign:2

Nov 20, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Atypical Gaucher Disease

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Gaucher disease due to saposin C deficiency

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Galactosylceramide beta-galactosidase deficiency

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hearing loss, autosomal recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa-deafness syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.60

dbscSNV1_RF

Benign

0.41

SpliceAI score (max)

0.020

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