NM_018238.4(AGK):c.1150_1154del (p.Phe383_Ser384insTer) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 23, 2024
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:: RCV003091648.4

Allele description [Variation Report for NM_018238.4(AGK):c.1150_1154del (p.Phe383_Ser384insTer)]

NM_018238.4(AGK):c.1150_1154del (p.Phe383_Ser384insTer)

Gene:

AGK:acylglycerol kinase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7q34

Genomic location:

Preferred name:

NM_018238.4(AGK):c.1150_1154del (p.Phe383_Ser384insTer)

HGVS:

NC_000007.14:g.141652805_141652809del
NG_032079.1:g.106528_106532del
NM_018238.4:c.1150_1154delMANE SELECT
NP_060708.1:p.Phe383_Ser384insTer
LRG_1251t1:c.1150_1154del
LRG_1251:g.106528_106532del
LRG_1251p1:p.Phe383_Ser384insTer
NC_000007.13:g.141352604_141352608del
NC_000007.13:g.141352605_141352609del

Links:

dbSNP: rs773677513

NCBI 1000 Genomes Browser:

rs773677513

Molecular consequence:

NM_018238.4:c.1150_1154del - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Sengers syndrome
Synonyms:: Cardiomyopathy and cataract; MITOCHONDRIAL DNA DEPLETION SYNDROME 10 (CARDIOMYOPATHIC TYPE)
Identifiers:: MONDO: MONDO:0008922; MedGen: C1859317; Orphanet: 1369; OMIM: 212350

Name:: Cataract 38
Synonyms:: Cataract, autosomal recessive congenital 5; Cataract 38, autosomal recessive
Identifiers:: MONDO: MONDO:0013859; MedGen: C3553494; Orphanet: 91492; OMIM: 614691

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003477459	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Feb 23, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22277967, 22284826, 31303091, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003477459

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Feb 23, 2024)

germline

clinical testing

PubMed (4)
[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

Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing.

Calvo SE, Compton AG, Hershman SG, Lim SC, Lieber DS, Tucker EJ, Laskowski A, Garone C, Liu S, Jaffe DB, Christodoulou J, Fletcher JM, Bruno DL, Goldblatt J, Dimauro S, Thorburn DR, Mootha VK.

Sci Transl Med. 2012 Jan 25;4(118):118ra10. doi: 10.1126/scitranslmed.3003310.

PubMed [citation]

PMID:: 22277967
PMCID:: PMC3523805

Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome.

Mayr JA, Haack TB, Graf E, Zimmermann FA, Wieland T, Haberberger B, Superti-Furga A, Kirschner J, Steinmann B, Baumgartner MR, Moroni I, Lamantea E, Zeviani M, Rodenburg RJ, Smeitink J, Strom TM, Meitinger T, Sperl W, Prokisch H.

Am J Hum Genet. 2012 Feb 10;90(2):314-20. doi: 10.1016/j.ajhg.2011.12.005. Epub 2012 Jan 26.

PubMed [citation]

PMID:: 22284826
PMCID:: PMC3276657

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003477459.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Ser384*) in the AGK gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 39 amino acid(s) of the AGK protein. This variant is present in population databases (rs773677513, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with AGK-related conditions. ClinVar contains an entry for this variant (Variation ID: 2163165). This variant disrupts the C-terminus of the AGK protein. Other variant(s) that disrupt this region (p.Tyr390*, p.Gln405*, p.Phe406Valfs*4) have been observed in individuals with AGK-related conditions (PMID: 22277967, 22284826, 31303091). This suggests that this may be a clinically significant region of the protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: May 16, 2025

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