NM_001253852.3(AP4B1):c.-2_4delinsGCCA (p.Met1fs) AND Inborn genetic diseases

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 12, 2016
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002313479.8

Allele description [Variation Report for NM_001253852.3(AP4B1):c.-2_4delinsGCCA (p.Met1fs)]

NM_001253852.3(AP4B1):c.-2_4delinsGCCA (p.Met1fs)

Genes:

LOC129931235:ATAC-STARR-seq lymphoblastoid active region 1540 [Gene]
DCLRE1B:DNA cross-link repair 1B [Gene - OMIM - HGNC]
AP4B1:adaptor related protein complex 4 subunit beta 1 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

1p13.2

Genomic location:

Preferred name:

NM_001253852.3(AP4B1):c.-2_4delinsGCCA (p.Met1fs)

HGVS:

NC_000001.11:g.113904714_113904719delinsTGGC
NG_031901.1:g.5401_5406delinsGCCA
NG_057565.1:g.5096_5101delinsTGGC
NG_164279.1:g.240_245delinsTGGC
NM_001253852.3:c.-2_4delinsGCCAMANE SELECT
NM_001253853.3:c.-171_-166delinsGCCA
NM_001308312.2:c.-2_4delinsGCCA
NM_001319947.2:c.-331+6_-331+11delinsTGGC
NM_006594.5:c.-2_4delinsGCCA
NP_001240781.1:p.Met1fs
NP_001295241.1:p.Met1fs
NP_006585.2:p.Met1fs
LRG_1219:g.5096_5101delinsTGGC
NC_000001.10:g.114447336_114447341delinsTGGC
NM_006594.2:c.-2_4delAGATGCinsGCCA
NM_006594.4:c.-2_4delinsGCCA

Protein change:

M1fs

Links:

dbSNP: rs1558100393

NCBI 1000 Genomes Browser:

rs1558100393

Molecular consequence:

NM_001253853.3:c.-171_-166delinsGCCA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001253852.3:c.-2_4delinsGCCA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001308312.2:c.-2_4delinsGCCA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006594.5:c.-2_4delinsGCCA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001253852.3:c.-2_4delinsGCCA - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001308312.2:c.-2_4delinsGCCA - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_006594.5:c.-2_4delinsGCCA - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001319947.2:c.-331+6_-331+11delinsTGGC - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000848451	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 12, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000848451

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 12, 2016)

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, SCV000848451.6

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

Description

The c.-2_4delAGATGCinsGCCA variant (also known as p.M1?) is located in 5'UTR to coding exon 1 of the AP4B1 gene and results from a replacement of AGATGC with GCCA at nucleotide positions -2 to 4. This alters the methionine residue at the initiation codon (ATG). Variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame; however there is methionine at amino acid position 40, which might be used as alternative initiation site. In addition, the significance of the N-terminus for this protein is not well established. Since supporting evidence is limited at this time, the clinical significance of this variant 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

Last Updated: Nov 30, 2024

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