rs774721609
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000287.4(PEX6):c.2730G>A(p.Thr910=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,614,020 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
PEX6
NM_000287.4 synonymous
NM_000287.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -6.81
Genes affected
PEX6 (HGNC:8859): (peroxisomal biogenesis factor 6) This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) family of ATPases. This member is a predominantly cytoplasmic protein, which plays a direct role in peroxisomal protein import and is required for PTS1 (peroxisomal targeting signal 1, a C-terminal tripeptide of the sequence ser-lys-leu) receptor activity. Mutations in this gene cause peroxisome biogenesis disorders of complementation group 4 and complementation group 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 6-42964866-C-T is Benign according to our data. Variant chr6-42964866-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-6.81 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX6 | NM_000287.4 | c.2730G>A | p.Thr910= | synonymous_variant | 16/17 | ENST00000304611.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX6 | ENST00000304611.13 | c.2730G>A | p.Thr910= | synonymous_variant | 16/17 | 1 | NM_000287.4 | P1 | |
PEX6 | ENST00000244546.4 | c.*266G>A | 3_prime_UTR_variant | 14/15 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152140Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251464Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135906
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461880Hom.: 0 Cov.: 34 AF XY: 0.0000261 AC XY: 19AN XY: 727240
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74330
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Peroxisome biogenesis disorder 4A (Zellweger);C3553937:Peroxisome biogenesis disorder 4B Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Apr 05, 2017 | - - |
Peroxisome biogenesis disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at