NM_001283.5(AP1S1):c.186T>G (p.Tyr62Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 12, 2022
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:: RCV000760751.6

Allele description [Variation Report for NM_001283.5(AP1S1):c.186T>G (p.Tyr62Ter)]

NM_001283.5(AP1S1):c.186T>G (p.Tyr62Ter)

Genes:

LOC126860125:BRD4-independent group 4 enhancer GRCh37_chr7:100799642-100800841 [Gene]
AP1S1:adaptor related protein complex 1 subunit sigma 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q22.1

Genomic location:

Preferred name:

NM_001283.5(AP1S1):c.186T>G (p.Tyr62Ter)

HGVS:

NC_000007.14:g.101157380T>G
NG_033082.2:g.7983T>G
NM_001283.5:c.186T>GMANE SELECT
NP_001274.1:p.Tyr62Ter
LRG_1363t1:c.186T>G
LRG_1363:g.7983T>G
LRG_1363p1:p.Tyr62Ter
NC_000007.13:g.100800661T>G
NM_001283.3:c.186T>G

Protein change:

Y62*

Links:

dbSNP: rs981747624

NCBI 1000 Genomes Browser:

rs981747624

Molecular consequence:

NM_001283.5:c.186T>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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serum paraoxonase/arylesterase 2 isoform X2 [Homo sapiens]
serum paraoxonase/arylesterase 2 isoform X2 [Homo sapiens]
gi|2462614938|ref|XP_054214451.1|

Protein
Sparus aurata mitochondrion sequence.
Sparus aurata mitochondrion sequence.
PopSet: 2553916987

PopSet
PopSet Links for Nucleotide (Select 2553917003) (1)
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Congestive heart failure
Congestive heart failure
Accession: GDS213

GEO DataSets
Related DataSets for GEO Profiles (Select 996340) (1)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000890645	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 12, 2022)	germline	clinical testing	Citation Link,
SCV003290664	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 2, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23423674, 1905767, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000890645

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 12, 2022)

germline

clinical testing

Citation Link,

SCV003290664

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 2, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Citations

PubMed

MEDNIK syndrome: a novel defect of copper metabolism treatable by zinc acetate therapy.

Martinelli D, Travaglini L, Drouin CA, Ceballos-Picot I, Rizza T, Bertini E, Carrozzo R, Petrini S, de Lonlay P, El Hachem M, Hubert L, Montpetit A, Torre G, Dionisi-Vici C.

Brain. 2013 Mar;136(Pt 3):872-81. doi: 10.1093/brain/awt012. Epub 2013 Feb 18. Erratum in: Brain. 2013 Oct;136(Pt 10):e256.

PubMed [citation]

PMID:: 23423674

Subrenal capsule assay using nude mice as a predictor of the response of the gastric cancer to chemotherapy.

Yamauchi M, Satta T, Ito A, Kondo K, Akiyama S, Ito K, Watanabe T, Takagi H.

J Surg Oncol. 1991 Jun;47(2):98-101.

PubMed [citation]

PMID:: 1905767

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000890645.4

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

Description

Has not been previously published as pathogenic or benign to our knowledge; Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD)

#	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 Invitae, SCV003290664.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 620377). This variant has not been reported in the literature in individuals affected with AP1S1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr62*) in the AP1S1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AP1S1 are known to be pathogenic (PMID: 23423674, 1905767).

#	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: Feb 14, 2024

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