ClinVar Genomic variation as it relates to human health
NM_181705.4(LYRM7):c.2T>C (p.Met1Thr)
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.
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(1); Likely pathogenic(2); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_181705.4(LYRM7):c.2T>C (p.Met1Thr)
Variation ID: 1323256 Accession: VCV001323256.8
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q23.3 5: 131171022 (GRCh38) [ NCBI UCSC ] 5: 130506715 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Nov 29, 2021 May 26, 2024 Jun 13, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_181705.4:c.2T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_859056.2:p.Met1Thr missense initiator codon variant NM_001293735.2:c.2T>C NP_001280664.1:p.Met1Thr missense initiator codon variant NR_121658.2:n.79T>C non-coding transcript variant NC_000005.10:g.131171022T>C NC_000005.9:g.130506715T>C NG_034163.1:g.5109T>C - Protein change
- M1T
- Other names
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- Canonical SPDI
- NC_000005.10:131171021:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00002
- Links
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 | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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LYRM7 | - | - |
GRCh38 GRCh37 |
72 | 93 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Jun 13, 2023 | RCV001783620.9 |
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
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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. |
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Likely pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial complex III deficiency nuclear type 8
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Lifecell International Pvt. Ltd
Accession: SCV003922037.2
First in ClinVar: May 06, 2023 Last updated: Sep 03, 2023 |
Comment:
A Homozygote Start lost variant c.2T>C in Exon 1 of the LYRM7 gene that results in the amino acid substitution p.Met1? was identified. The observed … (more)
A Homozygote Start lost variant c.2T>C in Exon 1 of the LYRM7 gene that results in the amino acid substitution p.Met1? was identified. The observed variant has a minor allele frequency of 0.00002% in gnomAD exomes and novel genomes, respectively. The severity of the impact of this variant on the protein is medium, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic (Variant ID: 1323256).This disorder has previously been reported in mitochorial cmplex II (Molina-Berenguer M et al 2022). Based on the above evidence this variant has been classified as Likely Pathogenic according to the ACMG guidelines. (less)
Ethnicity/Population group: Asian
Geographic origin: India
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Pathogenic
(Jun 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial complex III deficiency nuclear type 8
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
Accession: SCV004032530.1
First in ClinVar: Sep 16, 2023 Last updated: Sep 16, 2023 |
Sex: female
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Likely pathogenic
(Apr 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial complex III deficiency nuclear type 8
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002017195.4
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Uncertain significance
(-)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial complex III deficiency nuclear type 8
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004047194.2
First in ClinVar: Oct 28, 2023 Last updated: May 26, 2024 |
Comment:
The start lost variant c.2T>Cp.Met1? in the LYRM7 gene has been reported in homozygous state in an individual affected with mitochondrial complex III deficiency Alfattal … (more)
The start lost variant c.2T>Cp.Met1? in the LYRM7 gene has been reported in homozygous state in an individual affected with mitochondrial complex III deficiency Alfattal et al., 2023. This variant is reported with the allele frequency 0.001% in the gnomAD Exomes and novel not in any individuals in 1000 Genomes. The p.Met1? a variant is predicted to disrupt the initiation codon, and thus potentially may interfere with protein expression. This variant has been reported to the ClinVar database as Pathogenic. However, study on multiple affected individuals and functional studies on the pathogenicity of the variant is unavailable. This variant is predicted to cause a loss of normal protein function through protein truncation. Loss of function variants has been previously reported to be disease causing. For these reasons, this variant has been classified as Uncertain significance. (less)
Clinical Features:
Abnormality of the eye (present)
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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
HelpTitle | Author | Journal | Year | Link |
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LYRM7-associated mitochondrial complex III deficiency with non-cavitating leukoencephalopathy and stroke-like episodes. | Alfattal R | American journal of medical genetics. Part A | 2023 | PMID: 36757047 |
Dysfunctional mitochondrial translation and combined oxidative phosphorylation deficiency in a mouse model of hepatoencephalopathy due to Gfm1 mutations. | Molina-Berenguer M | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 2022 | PMID: 34919756 |
Text-mined citations for rs531275086 ...
HelpRecord last updated May 27, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.