rs753198978
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001164507.2(NEB):c.10268C>T(p.Pro3423Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,764 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P3423P) 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.10268C>T | p.Pro3423Leu | missense_variant | 70/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.10268C>T | p.Pro3423Leu | missense_variant | 70/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.10268C>T | p.Pro3423Leu | missense_variant | 70/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.10268C>T | p.Pro3423Leu | missense_variant | 70/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.9539C>T | p.Pro3180Leu | missense_variant | 67/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152080Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249204Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135186
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461684Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727124
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 152080Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74284
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 20, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 3423 of the NEB protein (p.Pro3423Leu). This variant is present in population databases (rs753198978, gnomAD 0.006%). 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: 447751). 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 09, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at