NM_002778.4(PSAP):c.623T>G (p.Ile208Ser) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 10, 2017
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000514444.5

Allele description [Variation Report for NM_002778.4(PSAP):c.623T>G (p.Ile208Ser)]

NM_002778.4(PSAP):c.623T>G (p.Ile208Ser)

Gene:

PSAP:prosaposin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q22.1

Genomic location:

Preferred name:

NM_002778.4(PSAP):c.623T>G (p.Ile208Ser)

HGVS:

NC_000010.11:g.71828111A>C
NG_009301.1:g.28215T>G
NM_001042465.3:c.623T>G
NM_001042466.3:c.623T>G
NM_002778.4:c.623T>GMANE SELECT
NP_001035930.1:p.Ile208Ser
NP_001035931.1:p.Ile208Ser
NP_002769.1:p.Ile208Ser
NC_000010.10:g.73587868A>C
NM_002778.2:c.623T>G
NM_002778.3:c.623T>G

Protein change:

I208S

Links:

dbSNP: rs200319381

NCBI 1000 Genomes Browser:

rs200319381

Molecular consequence:

NM_001042465.3:c.623T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001042466.3:c.623T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002778.4:c.623T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000610142	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 9, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000621587	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Oct 10, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000610142

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 9, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000621587

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Oct 10, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV000610142.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	0.000416	not provided	not provided

From GeneDx, SCV000621587.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The I208S variant in the PSAP gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I208S variant is observed in 160/34420 (0.46%) alleles from individuals of Latino background, in the ExAC dataset, an individuals were reported to be homozygous (Lek et al., 2016). The I208S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret I208S as a variant of uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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