rs1181510782
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001164507.2(NEB):āc.17627T>Cā(p.Leu5876Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,398 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. L5876L) 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.17627T>C | p.Leu5876Pro | missense_variant | 111/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.17627T>C | p.Leu5876Pro | missense_variant | 111/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.17627T>C | p.Leu5876Pro | missense_variant | 111/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.17627T>C | p.Leu5876Pro | missense_variant | 111/182 | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000419 AC: 1AN: 238450Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 128762
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1453398Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 722206
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 22, 2017 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Unavailable"; Align-GVGD: "Class C0"). While this variant is not present in population databases (Exac no frequency), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with an NEB-related disease. This sequence change replaces leucine with proline at codon 5876 of the NEB protein (p.Leu5876Pro). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and proline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at