13-24421229-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_006437.4(PARP4):c.5065C>T(p.Arg1689Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000442 in 1,381,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000047 ( 0 hom., cov: 26)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
PARP4
NM_006437.4 missense
NM_006437.4 missense
Scores
6
7
6
Clinical Significance
Conservation
PhyloP100: 2.26
Genes affected
PARP4 (HGNC:271): (poly(ADP-ribose) polymerase family member 4) This gene encodes poly(ADP-ribosyl)transferase-like 1 protein, which is capable of catalyzing a poly(ADP-ribosyl)ation reaction. This protein has a catalytic domain which is homologous to that of poly (ADP-ribosyl) transferase, but lacks an N-terminal DNA binding domain which activates the C-terminal catalytic domain of poly (ADP-ribosyl) transferase. Since this protein is not capable of binding DNA directly, its transferase activity may be activated by other factors such as protein-protein interaction mediated by the extensive carboxyl terminus. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.771
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PARP4 | NM_006437.4 | c.5065C>T | p.Arg1689Trp | missense_variant | 34/34 | ENST00000381989.4 | NP_006428.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PARP4 | ENST00000381989.4 | c.5065C>T | p.Arg1689Trp | missense_variant | 34/34 | 1 | NM_006437.4 | ENSP00000371419.3 | ||
TPTE2P6 | ENST00000445572.5 | n.233+11925G>A | intron_variant | 6 |
Frequencies
GnomAD3 genomes AF: 0.0000469 AC: 7AN: 149158Hom.: 0 Cov.: 26
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GnomAD3 exomes AF: 0.0000628 AC: 5AN: 79610Hom.: 0 AF XY: 0.0000762 AC XY: 3AN XY: 39356
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GnomAD4 exome AF: 0.0000438 AC: 54AN: 1232292Hom.: 0 Cov.: 20 AF XY: 0.0000364 AC XY: 22AN XY: 604622
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GnomAD4 genome AF: 0.0000469 AC: 7AN: 149158Hom.: 0 Cov.: 26 AF XY: 0.0000413 AC XY: 3AN XY: 72558
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2021 | The c.5065C>T (p.R1689W) alteration is located in exon 34 (coding exon 33) of the PARP4 gene. This alteration results from a C to T substitution at nucleotide position 5065, causing the arginine (R) at amino acid position 1689 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at