chr19-5678647-GC-G
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_205767.3(MICOS13):c.260delG(p.Gly87AlafsTer3) variant causes a frameshift, splice region change. The variant allele was found at a frequency of 0.00000458 in 1,529,544 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_205767.3 frameshift, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MICOS13 | NM_205767.3 | c.260delG | p.Gly87AlafsTer3 | frameshift_variant, splice_region_variant | Exon 4 of 4 | ENST00000309324.9 | NP_991330.1 | |
MICOS13 | NM_001308240.2 | c.326delG | p.Gly109AlafsTer3 | frameshift_variant, splice_region_variant | Exon 5 of 5 | NP_001295169.1 | ||
MICOS13 | NM_001365761.2 | c.326delG | p.Gly109AlafsTer3 | frameshift_variant, splice_region_variant | Exon 4 of 4 | NP_001352690.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MICOS13 | ENST00000309324.9 | c.260delG | p.Gly87AlafsTer3 | frameshift_variant, splice_region_variant | Exon 4 of 4 | 1 | NM_205767.3 | ENSP00000309561.3 | ||
MICOS13 | ENST00000587950.5 | c.326delG | p.Gly109AlafsTer3 | frameshift_variant, splice_region_variant | Exon 4 of 4 | 2 | ENSP00000468723.1 | |||
RPL36 | ENST00000579649.5 | c.-60+3665delC | intron_variant | Intron 1 of 4 | 5 | ENSP00000462609.1 | ||||
MICOS13 | ENST00000585605.1 | n.359delG | splice_region_variant, non_coding_transcript_exon_variant | Exon 4 of 4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152088Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000307 AC: 4AN: 130318Hom.: 0 AF XY: 0.0000291 AC XY: 2AN XY: 68810
GnomAD4 exome AF: 0.00000363 AC: 5AN: 1377456Hom.: 0 Cov.: 31 AF XY: 0.00000295 AC XY: 2AN XY: 678712
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152088Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74300
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Frameshift variant predicted to result in protein truncation, as the last 32 amino acids are replaced with 2 different amino acids, and another loss-of-function variant affecting the last exon has been reported in the published literature (PMID: 29618761); This variant is associated with the following publications: (PMID: 30912852) -
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. This variant has not been reported in the literature in individuals with C19orf70-related disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change results in a premature translational stop signal in the C19orf70 gene (p.Gly87Alafs*3). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 32 amino acids of the C19orf70 protein. The C19orf70 gene has multiple transcripts. The c.260delG (p.Gly87Alafs*3) variant occurs in alternate transcript NM_205767.2, which corresponds to c.326delG (p.Gly109Alafs*3) in NM_001308240.1, the primary transcript listed in the Methods. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at