rs142138590
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006393.3(NEBL):c.625G>T(p.Ala209Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A209T) has been classified as Uncertain significance.
Frequency
Consequence
NM_006393.3 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 |
---|---|---|---|---|---|---|---|
NEBL | NM_006393.3 | c.625G>T | p.Ala209Ser | missense_variant | 7/28 | ENST00000377122.9 | |
LOC102725112 | XR_007062082.1 | n.351+3256C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.625G>T | p.Ala209Ser | missense_variant | 7/28 | 1 | NM_006393.3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251150Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135728
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460478Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726658
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 24, 2014 | Variant classified as Uncertain Significance - Favor Benign. The Ala209Ser varia nt in NEBL has not been previously reported in individuals with cardiomyopathy o r in large population studies. Computational prediction tools and conservation analysis suggest that the Ala209Ser variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. Alanine (A la) at position 209 is not conserved in mammals or evolutionarily distant specie s and 5 mammals (Prairie vole, Chinese hamster, Golden hamster, Mouse, and Rat) carry a Serine (Ser) at this position, supporting that this change may be tolera ted. In summary, while the clinical significance of the Ala209Ser variant is u ncertain, these data suggest that it is more likely to be benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at