chrX-103785567-C-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000533.5(PLP1):c.5-15C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,090,805 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.000019 ( 0 hom. 14 hem. )
Failed GnomAD Quality Control
Consequence
PLP1
NM_000533.5 splice_polypyrimidine_tract, intron
NM_000533.5 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.282
Genes affected
PLP1 (HGNC:9086): (proteolipid protein 1) This gene encodes a transmembrane proteolipid protein that is the predominant component of myelin. The encoded protein may play a role in the compaction, stabilization, and maintenance of myelin sheaths, as well as in oligodendrocyte development and axonal survival. Mutations in this gene cause Pelizaeus-Merzbacher disease and spastic paraplegia type 2. Alternatively splicing results in multiple transcript variants, including the DM20 splice variant. [provided by RefSeq, Feb 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant X-103785567-C-G is Benign according to our data. Variant chrX-103785567-C-G is described in ClinVar as [Benign]. Clinvar id is 2978573.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000193 (21/1090805) while in subpopulation SAS AF= 0.000389 (21/53971). AF 95% confidence interval is 0.00026. There are 0 homozygotes in gnomad4_exome. There are 14 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAdExome at 8 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLP1 | NM_000533.5 | c.5-15C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000621218.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLP1 | ENST00000621218.5 | c.5-15C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000533.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 111309Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33501 FAILED QC
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GnomAD3 exomes AF: 0.0000601 AC: 11AN: 183057Hom.: 0 AF XY: 0.000118 AC XY: 8AN XY: 67553
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GnomAD4 exome AF: 0.0000193 AC: 21AN: 1090805Hom.: 0 Cov.: 29 AF XY: 0.0000392 AC XY: 14AN XY: 356933
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 111309Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33501
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at