rs756920047
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001164507.2(NEB):c.1648A>G(p.Lys550Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,738 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. K550K) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.1648A>G | p.Lys550Glu | missense_variant | 18/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.1648A>G | p.Lys550Glu | missense_variant | 18/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.1648A>G | p.Lys550Glu | missense_variant | 18/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.1648A>G | p.Lys550Glu | missense_variant | 18/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000489048.1 | n.547A>G | non_coding_transcript_exon_variant | 6/12 | 1 | ||||
NEB | ENST00000409198.5 | c.1648A>G | p.Lys550Glu | missense_variant | 18/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 249030Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135096
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461490Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727018
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74386
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces lysine with glutamic acid at codon 550 of the NEB protein (p.Lys550Glu). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamic acid. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. 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: 534024). 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 01, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at