3-122610693-C-G

Position:

• chr3-122610693-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001113523.3(PARP15):​c.506C>G​(p.Ala169Gly) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARP15 NM_001113523.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17

Genes affected

PARP15 (HGNC:26876): (poly(ADP-ribose) polymerase family member 15) Enables NAD+ binding activity; pentosyltransferase activity; and transcription corepressor activity. Involved in negative regulation of transcription by RNA polymerase II; protein mono-ADP-ribosylation; and protein poly-ADP-ribosylation. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PARP15 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15063676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP15	NM_001113523.3	c.506C>G	p.Ala169Gly	missense_variant	3/12	ENST00000464300.7	NP_001106995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP15	ENST00000464300.7	c.506C>G	p.Ala169Gly	missense_variant	3/12	1	NM_001113523.3	ENSP00000417214.2
PARP15	ENST00000483793.5	c.506C>G	p.Ala169Gly	missense_variant	3/9	1		ENSP00000417785.1
PARP15	ENST00000465304.5	n.482C>G		non_coding_transcript_exon_variant	4/14	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2023

The c.506C>G (p.A169G) alteration is located in exon 3 (coding exon 3) of the PARP15 gene. This alteration results from a C to G substitution at nucleotide position 506, causing the alanine (A) at amino acid position 169 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.88	D;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.32	N;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.8	D;N
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D;T
Sift4G	Benign	0.14	T;T
Polyphen		0.97	.;D
Vest4		0.23
MVP		0.11
MPC		0.28
ClinPred		0.90	D
GERP RS		4.4
Varity_R		0.23
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs778219932; hg19: chr3-122329540;