6-123366143-A-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006073.4(TRDN):c.1313T>A(p.Ile438Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 1,612,394 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I438S) has been classified as 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRDN | NM_006073.4 | c.1313T>A | p.Ile438Asn | missense_variant | Exon 20 of 41 | ENST00000334268.9 | NP_006064.2 | |
TRDN | NM_001251987.2 | c.1316T>A | p.Ile439Asn | missense_variant | Exon 20 of 21 | NP_001238916.1 | ||
TRDN | NM_001407315.1 | c.1256T>A | p.Ile419Asn | missense_variant | Exon 19 of 20 | NP_001394244.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRDN | ENST00000334268.9 | c.1313T>A | p.Ile438Asn | missense_variant | Exon 20 of 41 | 1 | NM_006073.4 | ENSP00000333984.5 | ||
TRDN | ENST00000662930.1 | c.1316T>A | p.Ile439Asn | missense_variant | Exon 20 of 21 | ENSP00000499585.1 |
Frequencies
GnomAD3 genomes AF: 0.00304 AC: 463AN: 152110Hom.: 12 Cov.: 32
GnomAD3 exomes AF: 0.00693 AC: 1719AN: 248196Hom.: 54 AF XY: 0.00680 AC XY: 916AN XY: 134654
GnomAD4 exome AF: 0.00268 AC: 3907AN: 1460166Hom.: 128 Cov.: 37 AF XY: 0.00280 AC XY: 2035AN XY: 726346
GnomAD4 genome AF: 0.00305 AC: 464AN: 152228Hom.: 12 Cov.: 32 AF XY: 0.00356 AC XY: 265AN XY: 74420
ClinVar
Submissions by phenotype
not specified Benign:5
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p.Ile438Asn in exon 20 of TRDN: This variant is not expected to have clinical si gnificance it has been identified in 8.1% (693/8588) of East Asian chromosomes, including 21 homozygotes, by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org; dbSNP rs2873479). -
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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. -
TRDN-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
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Cardiovascular phenotype Benign:1
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. -
Catecholaminergic polymorphic ventricular tachycardia 5 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at