rs377412251
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004006.3(DMD):c.4862T>C(p.Ile1621Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,208,449 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.4862T>C | p.Ile1621Thr | missense_variant | 35/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.4862T>C | p.Ile1621Thr | missense_variant | 35/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000631 AC: 7AN: 110917Hom.: 0 Cov.: 22 AF XY: 0.0000603 AC XY: 2AN XY: 33143
GnomAD3 exomes AF: 0.0000273 AC: 5AN: 182924Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67542
GnomAD4 exome AF: 0.00000729 AC: 8AN: 1097484Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1AN XY: 363028
GnomAD4 genome ? AF: 0.0000631 AC: 7AN: 110965Hom.: 0 Cov.: 22 AF XY: 0.0000602 AC XY: 2AN XY: 33201
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 19, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 14, 2017 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 23, 2023 | The p.I1621T variant (also known as c.4862T>C), located in coding exon 35 of the DMD gene, results from a T to C substitution at nucleotide position 4862. The isoleucine at codon 1621 is replaced by threonine, an amino acid with similar properties. Based on data from gnomAD, the C allele has an overall frequency of 0.003% (7/204627) total alleles studied, with 3 hemizygotes observed. The highest observed frequency was 0.04% (7/19054) of African/African American alleles. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Duchenne muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at