chr11-86450303-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The ENST00000393324.7(ME3):c.1015G>A(p.Glu339Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000393324.7 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ME3 | NM_001161586.3 | c.1015G>A | p.Glu339Lys | missense_variant, splice_region_variant | 9/15 | ENST00000543262.6 | |
ME3 | NR_172888.1 | n.1322G>A | splice_region_variant, non_coding_transcript_exon_variant | 9/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ME3 | ENST00000543262.6 | c.1015G>A | p.Glu339Lys | missense_variant, splice_region_variant | 9/15 | 1 | NM_001161586.3 | P1 | |
ENST00000524610.1 | n.268+17661C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250742Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135616
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461694Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4AN XY: 727154
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 15, 2023 | The c.1015G>A (p.E339K) alteration is located in exon 9 (coding exon 8) of the ME3 gene. This alteration results from a G to A substitution at nucleotide position 1015, causing the glutamic acid (E) at amino acid position 339 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at