rs6569336
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006073.4(TRDN):c.1408C>A(p.Leu470Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,422,180 control chromosomes in the GnomAD database, including 3,068 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L470L) has been classified as Likely benign.
Frequency
Consequence
NM_006073.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRDN | NM_006073.4 | c.1408C>A | p.Leu470Met | missense_variant | 22/41 | ENST00000334268.9 | |
LOC105377984 | XR_942947.3 | n.214-1G>T | splice_acceptor_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRDN | ENST00000334268.9 | c.1408C>A | p.Leu470Met | missense_variant | 22/41 | 1 | NM_006073.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0851 AC: 12923AN: 151898Hom.: 1783 Cov.: 32
GnomAD3 exomes AF: 0.0247 AC: 3225AN: 130400Hom.: 313 AF XY: 0.0240 AC XY: 1662AN XY: 69254
GnomAD4 exome AF: 0.0105 AC: 13318AN: 1270164Hom.: 1282 Cov.: 20 AF XY: 0.0112 AC XY: 7009AN XY: 628308
GnomAD4 genome ? AF: 0.0852 AC: 12946AN: 152016Hom.: 1786 Cov.: 32 AF XY: 0.0821 AC XY: 6103AN XY: 74326
ClinVar
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Leu470Met in exon 22 of TRDN: This variant is not expected to have clinical sign ificance because it has been identified in 25.2% (572/2268) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs6569336). - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 08, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 20, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 03, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 15, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at