rs746672297
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006904.7(PRKDC):āc.234T>Cā(p.Phe78=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00000376 in 1,594,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 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_006904.7 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.234T>C | p.Phe78= | splice_region_variant, synonymous_variant | 3/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.234T>C | p.Phe78= | splice_region_variant, synonymous_variant | 3/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.234T>C | p.Phe78= | splice_region_variant, synonymous_variant | 3/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.234T>C | p.Phe78= | splice_region_variant, synonymous_variant | 3/85 | 1 | |||
PRKDC | ENST00000540819.1 | c.-52T>C | splice_region_variant, 5_prime_UTR_variant | 3/5 | 3 | ||||
PRKDC | ENST00000697591.1 | n.275T>C | splice_region_variant, non_coding_transcript_exon_variant | 3/15 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000414 AC: 1AN: 241628Hom.: 0 AF XY: 0.00000762 AC XY: 1AN XY: 131158
GnomAD4 exome AF: 0.00000347 AC: 5AN: 1442324Hom.: 0 Cov.: 29 AF XY: 0.00000278 AC XY: 2AN XY: 718188
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74344
ClinVar
Submissions by phenotype
Severe combined immunodeficiency due to DNA-PKcs deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 17, 2018 | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change affects codon 78 of the PRKDC mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PRKDC protein. This variant is present in population databases (rs746672297, ExAC 0.02%). This variant has not been reported in the literature in individuals with PRKDC-related disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at