13-24431445-C-G

Variant names:

• chr13-24431445-C-G
• NM_006437.4:c.4778G>C

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 𝑓: 6.9e-7 (0 hom.)
• Consequence: PARP4 NM_006437.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59

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)

ACMG classification

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
PARP4	NM_006437.4	c.4778G>C	p.Gly1593Ala	missense_variant	Exon 32 of 34	ENST00000381989.4	NP_006428.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP4	ENST00000381989.4	c.4778G>C	p.Gly1593Ala	missense_variant	Exon 32 of 34	1	NM_006437.4	ENSP00000371419.3
TPTE2P6	ENST00000445572.5	n.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

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;