NM_000152.5(GAA):c.1536C>A (p.Phe512Leu) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jan 18, 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:: RCV000756197.12

Allele description [Variation Report for NM_000152.5(GAA):c.1536C>A (p.Phe512Leu)]

NM_000152.5(GAA):c.1536C>A (p.Phe512Leu)

Gene:

GAA:alpha glucosidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_000152.5(GAA):c.1536C>A (p.Phe512Leu)

HGVS:

NC_000017.11:g.80110825C>A
NG_009822.1:g.14270C>A
NM_000152.5:c.1536C>AMANE SELECT
NM_001079803.3:c.1536C>A
NM_001079804.3:c.1536C>A
NP_000143.2:p.Phe512Leu
NP_001073271.1:p.Phe512Leu
NP_001073272.1:p.Phe512Leu
LRG_673t1:c.1536C>A
LRG_673:g.14270C>A
NC_000017.10:g.78084624C>A
NM_000152.3:c.1536C>A

Protein change:

F512L

Links:

dbSNP: rs143491365

NCBI 1000 Genomes Browser:

rs143491365

Molecular consequence:

NM_000152.5:c.1536C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001079803.3:c.1536C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001079804.3:c.1536C>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Mus musculus protein phosphatase 6, regulatory subunit 1 (Ppp6r1), mRNA
Mus musculus protein phosphatase 6, regulatory subunit 1 (Ppp6r1), mRNA
gi|34536814|ref|NM_172894.2|

Nucleotide
Homo sapiens transmembrane protein 165, mRNA (cDNA clone MGC:132638 IMAGE:814398...
Homo sapiens transmembrane protein 165, mRNA (cDNA clone MGC:132638 IMAGE:8143981), complete cds
gi|85397069|gb|BC104978.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000582322	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (May 11, 2017)	germline	clinical testing	Citation Link,
SCV000883930	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (Jul 7, 2017)	germline	clinical testing	Citation Link,
SCV004224437	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 18, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000582322

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(May 11, 2017)

germline

clinical testing

Citation Link,

SCV000883930

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(Jul 7, 2017)

germline

clinical testing

Citation Link,

SCV004224437

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 18, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	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 GeneDx, SCV000582322.4

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

Description

The F512L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The F512L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved in mammals, and missense variants in nearby residues (G514R; M515K) have been reported in the Human Gene Mutation Database in association with GSDII (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.

#	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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000883930.1

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

Description

The p.Phe512Leu variant (rs143491365) has not been reported in the medical literature nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) Browser with an overall population frequency of 0.0004 percent (identified 1 out of 246,118 chromosomes). The phenylalanine at position 512 is moderately conserved considering twelve species from human to bakerâ€™s yeast (Alamut v2.9.0), and computational analyses of the effects of the p.Phe512Leu variant on protein structure and function is conflicting (SIFT: damaging, MutationTaster: polymorphism, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Phe512Leu variant with certainty.

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV004224437.1

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

Description

PM2

#	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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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