rs1159204491
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001164507.2(NEB):āc.1162A>Gā(p.Lys388Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. K388K) has been classified as Likely benign.
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.1162A>G | p.Lys388Glu | missense_variant | 14/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.1162A>G | p.Lys388Glu | missense_variant | 14/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.1162A>G | p.Lys388Glu | missense_variant | 14/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.1162A>G | p.Lys388Glu | missense_variant | 14/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000489048.1 | n.61A>G | non_coding_transcript_exon_variant | 2/12 | 1 | ||||
NEB | ENST00000409198.5 | c.1162A>G | p.Lys388Glu | missense_variant | 14/150 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1450264Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 721216
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 24, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 19, 2022 | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 388 of the NEB protein (p.Lys388Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NEB-related conditions. ClinVar contains an entry for this variant (Variation ID: 534009). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at