rs763012000
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001164507.2(NEB):āc.16958T>Cā(p.Met5653Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000683 in 1,611,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M5653L) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.16958T>C | p.Met5653Thr | missense_variant | 107/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.16958T>C | p.Met5653Thr | missense_variant | 107/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.16958T>C | p.Met5653Thr | missense_variant | 107/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.16958T>C | p.Met5653Thr | missense_variant | 107/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.11855T>C | p.Met3952Thr | missense_variant | 80/150 | 5 | |||
NEB | ENST00000413693.5 | c.1148T>C | p.Met383Thr | missense_variant | 7/74 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249064Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135122
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1458886Hom.: 0 Cov.: 29 AF XY: 0.00000826 AC XY: 6AN XY: 725958
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74370
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 | Oct 17, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 5653 of the NEB protein (p.Met5653Thr). This variant is present in population databases (rs763012000, 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: 465499). 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2021 | The c.11855T>C (p.M3952T) alteration is located in exon 80 (coding exon 78) of the NEB gene. This alteration results from a T to C substitution at nucleotide position 11855, causing the methionine (M) at amino acid position 3952 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 30, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at