8-17081693-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_181723.3(MICU3):c.647G>A(p.Gly216Asp) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000464 in 862,150 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
NM_181723.3 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 |
---|---|---|---|---|---|---|---|
MICU3 | NM_181723.3 | c.647G>A | p.Gly216Asp | missense_variant, splice_region_variant | 5/15 | ENST00000318063.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MICU3 | ENST00000318063.10 | c.647G>A | p.Gly216Asp | missense_variant, splice_region_variant | 5/15 | 1 | NM_181723.3 | P1 | |
MICU3 | ENST00000519044.5 | c.221G>A | p.Gly74Asp | missense_variant, splice_region_variant | 4/13 | 5 | |||
MICU3 | ENST00000517398.1 | c.167G>A | p.Gly56Asp | missense_variant, splice_region_variant | 4/4 | 3 | |||
MICU3 | ENST00000517447.1 | n.136G>A | splice_region_variant, non_coding_transcript_exon_variant | 4/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151870Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000884 AC: 1AN: 113150Hom.: 0 AF XY: 0.0000165 AC XY: 1AN XY: 60734
GnomAD4 exome AF: 0.00000282 AC: 2AN: 710280Hom.: 0 Cov.: 9 AF XY: 0.00000274 AC XY: 1AN XY: 364972
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151870Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74174
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 03, 2022 | The c.647G>A (p.G216D) alteration is located in exon 5 (coding exon 5) of the MICU3 gene. This alteration results from a G to A substitution at nucleotide position 647, causing the glycine (G) at amino acid position 216 to be replaced by an aspartic acid (D). 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