chr10-68122062-ATCT-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The NM_032578.4(MYPN):c.628_630delTCT(p.Ser210del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000013 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_032578.4 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.628_630delTCT | p.Ser210del | conservative_inframe_deletion | Exon 2 of 20 | ENST00000358913.10 | NP_115967.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251306Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135836
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461872Hom.: 0 AF XY: 0.0000124 AC XY: 9AN XY: 727242
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74334
ClinVar
Submissions by phenotype
not provided Uncertain:2
Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (gnomAD); In-frame deletion of one amino acid in a non-repeat region; In silico analysis supports that this variant does not alter protein structure/function -
The MYPN p.S210del variant was not identified in the literature but was identified in dbSNP (ID: rs749944961) and ClinVar (classified as uncertain significance by Ambry Genetics and Invitae). The variant was identified in control databases in 4 of 251306 chromosomes at a frequency of 0.00001592 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the European (non-Finnish) population in 4 of 113650 chromosomes (freq: 0.000035), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, or South Asian populations. This variant is an in-frame deletion resulting in the removal of a serine (S) residue at codon 210; the impact of this alteration on MYPN protein function is not known. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -
Dilated cardiomyopathy 1KK Uncertain:1
This variant, c.628_630del, results in the deletion of 1 amino acid(s) of the MYPN protein (p.Ser210del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs749944961, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with MYPN-related conditions. ClinVar contains an entry for this variant (Variation ID: 264245). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Cardiovascular phenotype Uncertain:1
The c.628_630delTCT variant (also known as p.S210del) is located in coding exon 1 of the MYPN gene. This variant results from the in-frame deletion of 3 nucleotides at positions 628 to 630. This results in the in-frame deletion of a serine residue at codon 210. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at