1-10474984-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004565.3(PEX14):āc.18G>Cā(p.Gln6His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 1,609,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q6E) has been classified as Uncertain significance.
Frequency
Consequence
NM_004565.3 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 |
---|---|---|---|---|---|---|---|
PEX14 | NM_004565.3 | c.18G>C | p.Gln6His | missense_variant | 1/9 | ENST00000356607.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX14 | ENST00000356607.9 | c.18G>C | p.Gln6His | missense_variant | 1/9 | 1 | NM_004565.3 | P1 | |
PEX14 | ENST00000491661.2 | c.3G>C | p.Gln1His | missense_variant | 1/6 | 2 | |||
PEX14 | ENST00000472851.1 | n.293+2404G>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000134 AC: 32AN: 239506Hom.: 0 AF XY: 0.000115 AC XY: 15AN XY: 130334
GnomAD4 exome AF: 0.000201 AC: 293AN: 1457556Hom.: 0 Cov.: 31 AF XY: 0.000199 AC XY: 144AN XY: 724632
GnomAD4 genome AF: 0.000177 AC: 27AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74378
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2023 | The c.18G>C (p.Q6H) alteration is located in exon 1 (coding exon 1) of the PEX14 gene. This alteration results from a G to C substitution at nucleotide position 18, causing the glutamine (Q) at amino acid position 6 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Peroxisome biogenesis disorder, complementation group K Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2022 | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 6 of the PEX14 protein (p.Gln6His). This variant is present in population databases (rs200395336, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PEX14-related conditions. ClinVar contains an entry for this variant (Variation ID: 500767). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 08, 2017 | - - |
Peroxisome biogenesis disorder 13A (Zellweger) Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 23, 2022 | - - |
PEX14-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 14, 2024 | The PEX14 c.18G>C variant is predicted to result in the amino acid substitution p.Gln6His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.024% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at