13-24431445-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006437.4(PARP4):​c.4778G>C​(p.Gly1593Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,443,490 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1593V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

PARP4
NM_006437.4 missense

Scores

1
11
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.59
Variant links:
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]
TPTE2P6 (HGNC:42644): (TPTE2 pseudogene 6)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PARP4NM_006437.4 linkc.4778G>C p.Gly1593Ala missense_variant Exon 32 of 34 ENST00000381989.4 NP_006428.2 Q9UKK3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PARP4ENST00000381989.4 linkc.4778G>C p.Gly1593Ala missense_variant Exon 32 of 34 1 NM_006437.4 ENSP00000371419.3 Q9UKK3
TPTE2P6ENST00000445572.5 linkn.233+22141C>G intron_variant Intron 3 of 9 6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.93e-7
AC:
1
AN:
1443490
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
717934
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.04e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T
Eigen
Uncertain
0.19
Eigen_PC
Benign
0.034
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.0075
T
MetaRNN
Uncertain
0.56
D
MetaSVM
Uncertain
0.22
D
MutationAssessor
Uncertain
2.7
M
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-3.3
D
REVEL
Uncertain
0.35
Sift
Uncertain
0.010
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.44
MutPred
0.41
Gain of catalytic residue at N1597 (P = 0);
MVP
0.94
MPC
0.58
ClinPred
0.97
D
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-25005583; API