19-49862568-C-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_007254.4(PNKP):c.906G>A(p.Lys302Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,606 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 Likely benign (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
PNKP
NM_007254.4 synonymous
NM_007254.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.958
Publications
0 publications found
Genes affected
PNKP (HGNC:9154): (polynucleotide kinase 3'-phosphatase) This locus represents a gene involved in DNA repair. In response to ionizing radiation or oxidative damage, the protein encoded by this locus catalyzes 5' phosphorylation and 3' dephosphorylation of nucleic acids. Mutations at this locus have been associated with microcephaly, seizures, and developmental delay.[provided by RefSeq, Sep 2010]
PNKP Gene-Disease associations (from GenCC):
- ataxia - oculomotor apraxia type 4Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, G2P, Orphanet
- microcephaly, seizures, and developmental delayInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
- Charcot-Marie-Tooth disease type 2B2Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
- genetic developmental and epileptic encephalopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 19-49862568-C-T is Benign according to our data. Variant chr19-49862568-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 515774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.958 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_007254.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PNKP | TSL:1 MANE Select | c.906G>A | p.Lys302Lys | synonymous | Exon 10 of 17 | ENSP00000323511.2 | Q96T60-1 | ||
| PNKP | TSL:1 | c.906G>A | p.Lys302Lys | synonymous | Exon 9 of 16 | ENSP00000472300.1 | Q96T60-1 | ||
| PNKP | TSL:1 | n.*833G>A | non_coding_transcript_exon | Exon 9 of 16 | ENSP00000468896.1 | M0QX49 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460606Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 726614 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460606
Hom.:
Cov.:
35
AF XY:
AC XY:
0
AN XY:
726614
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33454
American (AMR)
AF:
AC:
1
AN:
44610
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26082
East Asian (EAS)
AF:
AC:
0
AN:
39646
South Asian (SAS)
AF:
AC:
0
AN:
86168
European-Finnish (FIN)
AF:
AC:
0
AN:
53152
Middle Eastern (MID)
AF:
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111434
Other (OTH)
AF:
AC:
0
AN:
60298
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
-
1
Developmental and epileptic encephalopathy, 12 (1)
-
-
1
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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