rs1006402358

Variant names:

• chr13-24434781-A-T
• rs1006402358
• NM_006437.4:c.4360T>A

Your query was ambiguous. Multiple possible variants found:

• chr13-24434781-A-T
• chr13-24434781-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006437.4(PARP4):​c.4360T>A​(p.Tyr1454Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PARP4 NM_006437.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.08
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07881799).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP4	NM_006437.4	MANE Select	c.4360T>A	p.Tyr1454Asn	missense	Exon 31 of 34	NP_006428.2	Q9UKK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP4	ENST00000381989.4	TSL:1 MANE Select	c.4360T>A	p.Tyr1454Asn	missense	Exon 31 of 34	ENSP00000371419.3	Q9UKK3
	PARP4	ENST00000908086.1		c.4360T>A	p.Tyr1454Asn	missense	Exon 32 of 35	ENSP00000578145.1
	PARP4	ENST00000934618.1		c.4360T>A	p.Tyr1454Asn	missense	Exon 32 of 35	ENSP00000604677.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 246786 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460182 Hom.: 0 Cov.: 41 AF XY: 0.00000275 AC XY: 2 AN XY: 726322

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.0000225 AC: 1 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5386

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111332

Other (OTH) AF: 0.0000166 AC: 1 AN: 60300

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.0
DANN	Benign	0.61
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.038
Sift	Benign	0.28	T
Sift4G	Benign	0.31	T
Polyphen		0.043	B
Vest4		0.14
MutPred		0.23		Gain of catalytic residue at H1455 (P = 0)
MVP		0.35
MPC		0.20
ClinPred		0.041	T
GERP RS		-1.4
Varity_R		0.035
gMVP		0.10
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1006402358; hg19: chr13-25008919;