chr6-152208032-ACTCATGGGGAGGTAGGACACTTCAACCAACCATTTACGAAGCTTTTCTGCCATCT-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_182961.4(SYNE1):c.22709_22763delAGATGGCAGAAAAGCTTCGTAAATGGTTGGTTGAAGTGTCCTACCTCCCCATGAG(p.Glu7570fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_182961.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.22709_22763delAGATGGCAGAAAAGCTTCGTAAATGGTTGGTTGAAGTGTCCTACCTCCCCATGAG | p.Glu7570fs | frameshift_variant | 125/146 | ENST00000367255.10 | NP_892006.3 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461876Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727240
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 28, 2016 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 17, 2017 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 16, 2018 | A variant that is likely pathogenic has been identified in the SYNE1 gene. The c.22496_22550del55 variant in the SYNE1 gene causes a frameshift starting with codon Glutamic acid 7499, changes this amino acid to a Valine residue and creates a premature Stop codon at position 36 of the new reading frame, denoted p.Glu7499ValfsX36. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at