NM_030943.4(AMN):c.1161dup (p.Arg388fs) AND Imerslund-Grasbeck syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 17, 2023
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:: RCV003873006.1

Allele description [Variation Report for NM_030943.4(AMN):c.1161dup (p.Arg388fs)]

NM_030943.4(AMN):c.1161dup (p.Arg388fs)

Gene:

AMN:amnion associated transmembrane protein [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

14q32.32

Genomic location:

Preferred name:

NM_030943.4(AMN):c.1161dup (p.Arg388fs)

HGVS:

NC_000014.9:g.102930319dup
NG_008276.2:g.12664dup
NG_190975.1:g.402dup
NM_001425246.1:c.999dup
NM_030943.4:c.1161dupMANE SELECT
NP_001412175.1:p.Arg334Glufs
NP_112205.2:p.Arg388Glufs
NP_112205.2:p.Arg388fs
LRG_642t1:c.1161dup
LRG_642:g.12664dup
LRG_642p1:p.Arg388Glufs
NC_000014.8:g.103396652_103396653insG
NC_000014.8:g.103396656dup
NM_030943.3:c.1161dup

Protein change:

R388fs

Molecular consequence:

NM_001425246.1:c.999dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_030943.4:c.1161dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Imerslund-Grasbeck syndrome
Synonyms:: Megaloblastic anemia due to inborn errors of metabolism; Pernicious anemia, juvenile, due to selective intestinal malabsorption of vitamin b12, with proteinuria; Enterocyte cobalamin malabsorption; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009853; MedGen: C4551825; Orphanet: 35858; OMIM: PS261100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004674855	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 17, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22929189, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004674855

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 17, 2023)

germline

clinical testing

PubMed (2)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Inherited cobalamin malabsorption. Mutations in three genes reveal functional and ethnic patterns.

Tanner SM, Sturm AC, Baack EC, Liyanarachchi S, de la Chapelle A.

Orphanet J Rare Dis. 2012 Aug 28;7:56. doi: 10.1186/1750-1172-7-56.

PubMed [citation]

PMID:: 22929189
PMCID:: PMC3462684

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004674855.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change results in a frameshift in the AMN gene (p.Arg388Glufs*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 66 amino acid(s) of the AMN protein and extend the protein by an uncertain number of additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AMN-related conditions. This variant results in an extension of the AMN protein. Other variant(s) that result in a similarly extended protein product (p.His438Glnfs*) have been determined to be pathogenic (PMID: 22929189). This suggests that these extensions are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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: Mar 5, 2024

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