chr19-6361597-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006012.4(CLPP):c.23G>T(p.Gly8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,413,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. G8A) has been classified as Uncertain significance.
Frequency
Consequence
NM_006012.4 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 |
---|---|---|---|---|---|---|---|
CLPP | NM_006012.4 | c.23G>T | p.Gly8Val | missense_variant | 1/6 | ENST00000245816.11 | |
CLPP | XM_047439486.1 | c.23G>T | p.Gly8Val | missense_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLPP | ENST00000245816.11 | c.23G>T | p.Gly8Val | missense_variant | 1/6 | 1 | NM_006012.4 | P1 | |
ENST00000595644.1 | n.35+518C>A | intron_variant, non_coding_transcript_variant | 4 | ||||||
CLPP | ENST00000596070.1 | n.33G>T | non_coding_transcript_exon_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000103 AC: 13AN: 1261194Hom.: 0 Cov.: 31 AF XY: 0.00000819 AC XY: 5AN XY: 610774
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74348
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1370265). This variant has not been reported in the literature in individuals affected with CLPP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 8 of the CLPP protein (p.Gly8Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at