3-122692331-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_017554.3(PARP14):c.386C>G(p.Pro129Arg) 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. 15/21 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: PARP14 NM_017554.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0160

Genes affected

PARP14 (HGNC:29232): (poly(ADP-ribose) polymerase family member 14) This gene encodes a member of the poly(ADP-ribose) polymerase (PARP) protein family. The encoded anti-apoptotic protein may regulate aerobic glycolysis and promote survival of cancer cells. Increased expression of this gene has been reported in a variety of tumor types. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, PARP14
• BP4: Computational evidence support a benign effect (MetaRNN=0.085057616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP14	NM_017554.3	c.386C>G	p.Pro129Arg	missense_variant	4/17	ENST00000474629.7
PARP14	XM_011512929.3	c.386C>G	p.Pro129Arg	missense_variant	4/10
PARP14	XR_007095695.1	n.431C>G		non_coding_transcript_exon_variant	4/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP14	ENST00000474629.7	c.386C>G	p.Pro129Arg	missense_variant	4/17	1	NM_017554.3	P1
PARP14	ENST00000494811.2	c.356-3095C>G		intron_variant		4
PARP14	ENST00000483611.1	n.386C>G		non_coding_transcript_exon_variant	2/2	3
PARP14	ENST00000649945.1	c.386C>G	p.Pro129Arg	missense_variant, NMD_transcript_variant	4/16

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

Jan 03, 2024

The c.386C>G (p.P129R) alteration is located in exon 4 (coding exon 4) of the PARP14 gene. This alteration results from a C to G substitution at nucleotide position 386, causing the proline (P) at amino acid position 129 to be replaced by an arginine (R). 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	0.089
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	6.5
Dann	Benign	0.69
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.043
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.060	T
Polyphen		0.20	B
Vest4		0.067
MutPred		0.20		Loss of glycosylation at T126 (P = 0.036);
MVP		0.40
MPC		0.21
ClinPred		0.093	T
GERP RS		4.2
Varity_R		0.046
gMVP		0.17

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: chr3-122411178;