chrX-103776965-C-T
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_000533.5(PLP1):c.-31C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,197,630 control chromosomes in the GnomAD database, including 10 homozygotes. There are 543 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000533.5 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLP1 | NM_000533.5 | c.-31C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 7 | ENST00000621218.5 | NP_000524.3 | ||
PLP1 | NM_000533.5 | c.-31C>T | 5_prime_UTR_variant | Exon 1 of 7 | ENST00000621218.5 | NP_000524.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLP1 | ENST00000621218 | c.-31C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 7 | 1 | NM_000533.5 | ENSP00000484450.1 | |||
PLP1 | ENST00000621218 | c.-31C>T | 5_prime_UTR_variant | Exon 1 of 7 | 1 | NM_000533.5 | ENSP00000484450.1 |
Frequencies
GnomAD3 genomes AF: 0.00183 AC: 204AN: 111767Hom.: 1 Cov.: 23 AF XY: 0.00177 AC XY: 60AN XY: 33973
GnomAD3 exomes AF: 0.00343 AC: 619AN: 180671Hom.: 3 AF XY: 0.00243 AC XY: 159AN XY: 65353
GnomAD4 exome AF: 0.00144 AC: 1566AN: 1085813Hom.: 8 Cov.: 27 AF XY: 0.00136 AC XY: 481AN XY: 352643
GnomAD4 genome AF: 0.00190 AC: 213AN: 111817Hom.: 2 Cov.: 23 AF XY: 0.00182 AC XY: 62AN XY: 34033
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 13, 2021 | See Variant Classification Assertion Criteria. - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 19, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 18, 2017 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Pelizaeus-Merzbacher disease, mild Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Jan 01, 1996 | - - |
Hereditary spastic paraplegia 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 23, 2023 | - - |
Pelizaeus-Merzbacher disease;C1839264:Hereditary spastic paraplegia 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 25, 2022 | - - |
Pelizaeus-Merzbacher disease Benign:1
Benign, criteria provided, single submitter | research | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | - | The hemizygous c.-31C>T variant in PLP1 has been identified in a Japanese individual with Perlizaeus-Merzbacher disease (PMID: 8723686), and has been identified in >2% of East Asian chromosomes, 61 hemizygotes, and 1 homozygote by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for X-linked recessive Perlizaeus-Merzbacher disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at