chr19-6361602-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_006012.4(CLPP):c.28G>T(p.Ala10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000092 in 1,412,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. A10G) has been classified as Uncertain significance.
Frequency
Consequence
NM_006012.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLPP | NM_006012.4 | c.28G>T | p.Ala10Ser | missense_variant | 1/6 | ENST00000245816.11 | |
CLPP | XM_047439486.1 | c.28G>T | p.Ala10Ser | missense_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLPP | ENST00000245816.11 | c.28G>T | p.Ala10Ser | missense_variant | 1/6 | 1 | NM_006012.4 | P1 | |
ENST00000595644.1 | n.35+513C>A | intron_variant, non_coding_transcript_variant | 4 | ||||||
CLPP | ENST00000596070.1 | n.38G>T | non_coding_transcript_exon_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000587 AC: 3AN: 51094Hom.: 0 AF XY: 0.0000767 AC XY: 2AN XY: 26086
GnomAD4 exome AF: 0.00000635 AC: 8AN: 1260326Hom.: 0 Cov.: 31 AF XY: 0.00000655 AC XY: 4AN XY: 610408
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 10 of the CLPP protein (p.Ala10Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CLPP-related conditions. ClinVar contains an entry for this variant (Variation ID: 1301278). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 31, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at