rs534735519
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006904.7(PRKDC):c.1337T>A(p.Phe446Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,613,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F446L) has been classified as Likely benign.
Frequency
Consequence
NM_006904.7 missense
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.1337T>A | p.Phe446Tyr | missense_variant | 13/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.1337T>A | p.Phe446Tyr | missense_variant | 13/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.1337T>A | p.Phe446Tyr | missense_variant | 13/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.1337T>A | p.Phe446Tyr | missense_variant | 13/85 | 1 | |||
PRKDC | ENST00000697591.1 | n.1378T>A | non_coding_transcript_exon_variant | 13/15 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249246Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135220
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461670Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727130
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74484
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2021 | The c.1337T>A (p.F446Y) alteration is located in exon 13 (coding exon 13) of the PRKDC gene. This alteration results from a T to A substitution at nucleotide position 1337, causing the phenylalanine (F) at amino acid position 446 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Severe combined immunodeficiency due to DNA-PKcs deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 08, 2022 | This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 446 of the PRKDC protein (p.Phe446Tyr). This variant is present in population databases (rs534735519, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with PRKDC-related conditions. ClinVar contains an entry for this variant (Variation ID: 475217). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at