rs373800401
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_001042702.5(PJVK):āc.405A>Cā(p.Thr135=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,612,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001042702.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PJVK | NM_001042702.5 | c.405A>C | p.Thr135= | splice_region_variant, synonymous_variant | 3/7 | ENST00000644580.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PJVK | ENST00000644580.2 | c.405A>C | p.Thr135= | splice_region_variant, synonymous_variant | 3/7 | NM_001042702.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000604 AC: 15AN: 248180Hom.: 0 AF XY: 0.0000520 AC XY: 7AN XY: 134702
GnomAD4 exome AF: 0.000125 AC: 182AN: 1460596Hom.: 0 Cov.: 30 AF XY: 0.000111 AC XY: 81AN XY: 726632
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74354
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 59 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 15, 2013 | Thr135Thr in Exon 3 of DFNB59: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and, although it is lo cated 3 bp away from the exon/intron junction, computational tools do not sugges t an impact to splicing. The variant has been identified in 0.03% (3/8600) of E uropean American chromosomes by the NHLBI Exome Sequencing Project (http://evs.g s.washington.edu/EVS/; dbSNP rs20098046). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
PJVK-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 19, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at