rs1050112

Variant names:

• chr13-24435159-G-A
• rs1050112
• NM_006437.4:c.3982C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-24435159-G-A
• chr13-24435159-G-C
• chr13-24435159-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006437.4(PARP4):​c.3982C>T​(p.Pro1328Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PARP4 NM_006437.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063343585).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006437.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP4	NM_006437.4	MANE Select	c.3982C>T	p.Pro1328Ser	missense	Exon 31 of 34	NP_006428.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP4	ENST00000381989.4	TSL:1 MANE Select	c.3982C>T	p.Pro1328Ser	missense	Exon 31 of 34	ENSP00000371419.3
	TPTE2P6	ENST00000445572.5	TSL:6	n.233+25855G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.077
DANN	Benign	0.74
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.00070	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.9
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.039
Sift	Benign	0.67	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.046
MutPred		0.30		Gain of catalytic residue at G1324 (P = 0.007)
MVP		0.28
MPC		0.12
ClinPred		0.054	T
GERP RS		-4.7
Varity_R		0.014
gMVP		0.20
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1050112; hg19: chr13-25009297; COSMIC: COSV105311433;