rs373671419
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBP6
The NM_170707.4(LMNA):c.1657G>A(p.Asp553Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000296 in 1,555,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D553H) has been classified as Uncertain significance.
Frequency
Consequence
NM_170707.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LMNA | NM_170707.4 | c.1657G>A | p.Asp553Asn | missense_variant | 10/12 | ENST00000368300.9 | |
LMNA | NM_005572.4 | c.1657G>A | p.Asp553Asn | missense_variant | 10/10 | ENST00000677389.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMNA | ENST00000368300.9 | c.1657G>A | p.Asp553Asn | missense_variant | 10/12 | 1 | NM_170707.4 | P1 | |
LMNA | ENST00000677389.1 | c.1657G>A | p.Asp553Asn | missense_variant | 10/10 | NM_005572.4 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000984 AC: 16AN: 162670Hom.: 0 AF XY: 0.000128 AC XY: 11AN XY: 85804
GnomAD4 exome AF: 0.0000164 AC: 23AN: 1403638Hom.: 0 Cov.: 31 AF XY: 0.0000245 AC XY: 17AN XY: 692560
GnomAD4 genome AF: 0.000151 AC: 23AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74340
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published in association with an LMNA-related disorder to our knowledge; This variant is associated with the following publications: (PMID: 10939567, 28679633, 27884249) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 12, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 20, 2021 | - - |
Charcot-Marie-Tooth disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Arrhythmogenic right ventricular cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | Nov 29, 2016 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 10, 2019 | The p.Asp553Asn variant in LMNA is classified as likely benign because it has been identified in 0.06% (15/24926) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org). Additionally, 2 mammals (rat and mouse) have an asparagine (Asn) at this position despite relatively nearby amino acid conservation. In addition, most computational tools do not suggest a high likelihood of impact to the protein. ACMG/AMP Criteria applied: BS1_supporting, BP4. - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Oct 18, 2019 | - - |
Charcot-Marie-Tooth disease type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at