NM_003619.4(PRSS12):c.450C>A (p.Phe150Leu) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 8, 2023
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:: RCV003479487.2

Allele description [Variation Report for NM_003619.4(PRSS12):c.450C>A (p.Phe150Leu)]

NM_003619.4(PRSS12):c.450C>A (p.Phe150Leu)

Gene:

PRSS12:serine protease 12 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q26

Genomic location:

Preferred name:

NM_003619.4(PRSS12):c.450C>A (p.Phe150Leu)

HGVS:

NC_000004.12:g.118352271G>T
NG_023350.1:g.5497C>A
NM_003619.4:c.450C>AMANE SELECT
NP_003610.2:p.Phe150Leu
NC_000004.11:g.119273426G>T
NM_003619.3:c.450C>A

Protein change:

F150L

Molecular consequence:

NM_003619.4:c.450C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

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Mus musculus mannosidase 2, alpha B1 (Man2b1), transcript variant 2, mRNA
Mus musculus mannosidase 2, alpha B1 (Man2b1), transcript variant 2, mRNA
gi|2592185369|ref|NM_001424841.1|

Nucleotide
arylsulfatase K isoform 3 [Mus musculus]
arylsulfatase K isoform 3 [Mus musculus]
gi|2224096270|ref|NP_001391828.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003561701	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 18, 2021)	germline	clinical testing	Citation Link,
SCV004223529	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Nov 8, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003561701

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 18, 2021)

germline

clinical testing

Citation Link,

SCV004223529

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Nov 8, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Ambry Genetics, SCV003561701.2

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

Description

The c.450C>A (p.F150L) alteration is located in exon 1 (coding exon 1) of the PRSS12 gene. This alteration results from a C to A substitution at nucleotide position 450, causing the phenylalanine (F) at amino acid position 150 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004223529.1

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

Description

Variant summary: PRSS12 c.450C>A (p.Phe150Leu) results in a non-conservative amino acid change located in the Kringle (IPR000001) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.7e-05 in 239702 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.450C>A in individuals affected with Intellectual Disability, Autosomal Recessive 1 and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Nov 10, 2024

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