3-122610505-T-G

Position:

• chr3-122610505-T-G

Variant summary

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

The NM_001113523.3(PARP15):​c.318T>G​(p.Ile106Met) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARP15 NM_001113523.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0910

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 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
PARP15	NM_001113523.3	c.318T>G	p.Ile106Met	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.318T>G	p.Ile106Met	missense_variant	3/12	1	NM_001113523.3	ENSP00000417214.2
PARP15	ENST00000483793.5	c.318T>G	p.Ile106Met	missense_variant	3/9	1		ENSP00000417785.1
PARP15	ENST00000465304.5	n.294T>G		non_coding_transcript_exon_variant	4/14	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jul 17, 2024

The c.318T>G (p.I106M) alteration is located in exon 3 (coding exon 3) of the PARP15 gene. This alteration results from a T to G substitution at nucleotide position 318, causing the isoleucine (I) at amino acid position 106 to be replaced by a methionine (M). 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	0.15
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0067	T
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Pathogenic	3.4	M;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.35
Sift	Benign	0.058	T;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.98	.;D
Vest4		0.41
MVP		0.70
MPC		0.29
ClinPred		0.88	D
GERP RS		2.0
Varity_R		0.067
gMVP		0.55

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: chr3-122329352;