rs1805415

Positions:

• chr1-226383139-T-A
• chr1-226383139-T-C
• chr1-226383139-T-G

Variant summary

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

The NM_001618.4(PARP1):​c.1056A>T​(p.Lys352Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K352K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: PARP1 NM_001618.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

Genes affected

PARP1 (HGNC:270): (poly(ADP-ribose) polymerase 1) This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes. [provided by RefSeq, Jul 2008]

PARP1 (HGNC:):

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/exons	MANE	Protein	UniProt
PARP1	NM_001618.4	c.1056A>T	p.Lys352Asn	missense_variant	8/23	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.1056A>T	p.Lys352Asn	missense_variant	8/23	1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.71
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0096	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.078
Sift	Benign	0.49	T
Sift4G	Benign	0.49	T
Polyphen		0.078	B
Vest4		0.38
MutPred		0.32		Loss of methylation at K352 (P = 0.0094);
MVP		0.60
MPC		0.34
ClinPred		0.19	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1805415; hg19: chr1-226570840;