VCV000143993.8 - ClinVar

NM_022773.4(LMF1):c.1391G>A (p.Trp464Ter)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(6)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_022773.4(LMF1):c.1391G>A (p.Trp464Ter)

Variation ID: 143993 Accession: VCV000143993.8

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16p13.3 16: 869908 (GRCh38) [ NCBI UCSC ] 16: 919908 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Aug 24, 2014	Apr 6, 2024	Mar 29, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_022773.4:c.1391G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_073610.2:p.Trp464Ter	nonsense
NM_001352017.2:c.740G>A	NP_001338946.1:p.Trp247Ter	nonsense
NM_001352018.2:c.992G>A	NP_001338947.1:p.Trp331Ter	nonsense
NM_001352019.2:c.1064G>A	NP_001338948.1:p.Trp355Ter	nonsense
NM_001352020.1:c.1336+55G>A		intron variant
NM_001352021.2:c.740G>A	NP_001338950.1:p.Trp247Ter	nonsense
NR_147885.2:n.1395G>A		non-coding transcript variant
NC_000016.10:g.869908C>T
NC_000016.9:g.919908C>T
NG_021286.2:g.116708G>A

... more HGVS ... less HGVS

Protein change

W464*, W247*, W331*, W355*

Other names

Canonical SPDI

NC_000016.10:869907:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00000

The Genome Aggregation Database (gnomAD) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00002

Links

ClinGen: CA170562 OMIM: 611761.0002 dbSNP: rs587777626 VarSome

Comment on variant

NCBI staff reviewed the sequence information reported in PubMed 19820022 Fig. 2A to determine the location of this allele on the current reference sequence.

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
LMF1		-	-	GRCh38 GRCh37	505	645

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Lipase deficiency, combined	Pathogenic (6)	criteria provided, multiple submitters, no conflicts	Mar 29, 2024	RCV000133508.12

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jan 17, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Lipase deficiency, combined Affected status: yes Allele origin: unknown	Baylor Genetics Accession: SCV001521479.1 First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021	Comment: This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Pathogenic (May 04, 2022)	criteria provided, single submitter (Mendelics Assertion Criteria 2019) Method: clinical testing	Lipase deficiency, combined Affected status: unknown Allele origin: germline	Mendelics Accession: SCV002517567.1 First in ClinVar: May 28, 2022 Last updated: May 28, 2022
Pathogenic (Jun 06, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Lipase deficiency, combined Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV002017152.3 First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024
Pathogenic (Mar 29, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Lipase deficiency, combined Affected status: unknown Allele origin: germline	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center Accession: SCV004808293.1 First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024
Pathogenic (Nov 01, 2009)	no assertion criteria provided Method: literature only	LIPASE DEFICIENCY, COMBINED Affected status: not provided Allele origin: germline	OMIM Accession: SCV000188582.1 First in ClinVar: Aug 24, 2014 Last updated: Aug 24, 2014	Publications: PubMed (1) PubMed: 19820022 Hamosh, A. Personal Communication. (more...) Hamosh, A. Personal Communication. 2014. Baltimore, Md. Comment on evidence: In a patient with combined lipase deficiency (246650) and severe hypertriglyceridemia, Cefalu et al. (2009) identified homozygosity for a c.1359G-A transition in exon 9 of … (more) In a patient with combined lipase deficiency (246650) and severe hypertriglyceridemia, Cefalu et al. (2009) identified homozygosity for a c.1359G-A transition in exon 9 of the LMF1 gene, resulting in a trp464-to-ter (W464X) substitution. The authors found that this mutation showed significant reduction of LPL activity and specific Lmf1 activity but did not result in complete inactivation, as seen with the Y439X mutation (611761.0001). The W464X mutation was not found in the Exome Variant Server database (Hamosh, 2014). (less)
Pathogenic (Sep 10, 2020)	no assertion criteria provided Method: clinical testing	Lipase deficiency, combined Affected status: yes Allele origin: germline	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City Accession: SCV001469203.1 First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Novel LMF1 nonsense mutation in a patient with severe hypertriglyceridemia.	Cefalù AB	The Journal of clinical endocrinology and metabolism	2009	PMID: 19820022
Hamosh, A. Personal Communication. 2014. Baltimore, Md.	-	-	-	-

Text-mined citations for rs587777626 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 04, 2024

ClinVar Genomic variation as it relates to human health

NM_022773.4(LMF1):c.1391G>A (p.Trp464Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs587777626 ...