rs1057516758
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001164507.2(NEB):βc.6078delβ(p.Lys2026AsnfsTer62) variant causes a frameshift, splice region change. The variant allele was found at a frequency of 0.000000697 in 1,435,286 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (β β ). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001164507.2 frameshift, splice_region
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 | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.6078del | p.Lys2026AsnfsTer62 | frameshift_variant, splice_region_variant | 48/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.6078del | p.Lys2026AsnfsTer62 | frameshift_variant, splice_region_variant | 48/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.6078del | p.Lys2026AsnfsTer62 | frameshift_variant, splice_region_variant | 48/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.6078del | p.Lys2026AsnfsTer62 | frameshift_variant, splice_region_variant | 48/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.6078del | p.Lys2026AsnfsTer62 | frameshift_variant, splice_region_variant | 48/150 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.97e-7 AC: 1AN: 1435286Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 713798
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 370777). This premature translational stop signal has been observed in individual(s) with nemaline myopathy (PMID: 16917880, 25205138). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys2026Asnfs*62) in the NEB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NEB are known to be pathogenic (PMID: 25205138). - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Apr 12, 2016 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 09, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at