1-6475486-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_020631.6(PLEKHG5):c.186G>A(p.Lys62=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,613,446 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 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
PLEKHG5
NM_020631.6 synonymous
NM_020631.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.26
Genes affected
PLEKHG5 (HGNC:29105): (pleckstrin homology and RhoGEF domain containing G5) This gene encodes a protein that activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in this gene are associated with autosomal recessive distal spinal muscular atrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
?
Variant 1-6475486-C-T is Benign according to our data. Variant chr1-6475486-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 381312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-6475486-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=2.26 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHG5 | NM_020631.6 | c.186G>A | p.Lys62= | synonymous_variant | 4/21 | ENST00000377728.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHG5 | ENST00000377728.8 | c.186G>A | p.Lys62= | synonymous_variant | 4/21 | 2 | NM_020631.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000724 AC: 11AN: 151890Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249526Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135200
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GnomAD4 exome AF: 0.000135 AC: 198AN: 1461556Hom.: 0 Cov.: 32 AF XY: 0.000128 AC XY: 93AN XY: 727080
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Neuronopathy, distal hereditary motor, autosomal recessive 4;C3809309:Charcot-Marie-Tooth disease recessive intermediate C Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 06, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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