Genetic Variant PNKP:c.1386+49_1387-33dupCCTCCTCCCCTGACCCC (chr19-49861542-A-AGGGGTCAGGGGAGGAGG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_007254.4(PNKP):c.1386+49_1387-33dupCCTCCTCCCCTGACCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 682,792 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000052 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

PNKP
NM_007254.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.939

Publications

1 publications found

Variant links:

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 4
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P, Laboratory for Molecular Medicine
microcephaly, seizures, and developmental delay
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Charcot-Marie-Tooth disease type 2B2
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PNKP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNKP	NM_007254.4 link	c.1386+49_1387-33dupCCTCCTCCCCTGACCCC		intron_variant	Intron 15 of 16	ENST00000322344.8	NP_009185.2	Q96T60-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNKP	ENST00000322344.8 link	c.1386+49_1387-33dupCCTCCTCCCCTGACCCC		intron_variant	Intron 15 of 16	1	NM_007254.4	ENSP00000323511.2		Q96T60-1

Frequencies

GnomAD3 genomes

AF:

0.0000515

AC:

AN:

38800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000776

AC:

AN:

643992

Hom.:

Cov.:

AF XY:

0.0000156

AC XY:

AN XY:

319630

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15210

American (AMR)

AF:

0.00

AC:

AN:

22756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9800

East Asian (EAS)

AF:

0.000352

AC:

AN:

11376

South Asian (SAS)

AF:

0.00

AC:

AN:

45722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1870

European-Non Finnish (NFE)

AF:

0.00000204

AC:

AN:

491218

Other (OTH)

AF:

0.00

AC:

AN:

23624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000515

AC:

AN:

38800

Hom.:

Cov.:

AF XY:

0.0000511

AC XY:

AN XY:

19570

show subpopulations

African (AFR)

AF:

0.000203

AC:

AN:

9870

American (AMR)

AF:

0.00

AC:

AN:

3904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1004

East Asian (EAS)

AF:

0.00

AC:

AN:

1616

South Asian (SAS)

AF:

0.00

AC:

AN:

1242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1476

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

18764

Other (OTH)

AF:

0.00

AC:

AN:

584

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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19-49861542-AGGGGTCAGGGGAGGAGG-AGGGGTCAGGGGAGGAGGGGGGTCAGGGGAGGAGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over