chr8-37762691-T-TG
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_007198.4(PLPBP):c.35dup(p.Val13SerfsTer76) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000417 in 1,438,416 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L11L) has been classified as Likely benign.
Frequency
Consequence
NM_007198.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLPBP | NM_007198.4 | c.35dup | p.Val13SerfsTer76 | frameshift_variant | 1/8 | ENST00000328195.8 | |
LOC124901934 | XR_007060889.1 | n.460_461insC | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLPBP | ENST00000328195.8 | c.35dup | p.Val13SerfsTer76 | frameshift_variant | 1/8 | 1 | NM_007198.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000417 AC: 6AN: 1438416Hom.: 0 Cov.: 33 AF XY: 0.00000560 AC XY: 4AN XY: 713954
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 28, 2022 | The c.35dupG (p.V13Sfs*76) alteration, located in exon 1 (coding exon 1) of the PROSC gene, consists of a duplication of G at position 35, causing a translational frameshift with a predicted alternate stop codon after 76 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.