3-122699848-A-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_017554.3(PARP14):c.1294A>G(p.Met432Val) 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: 33)
• Consequence: PARP14 NM_017554.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.199

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 Likely_benign. 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=0.020763487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP14	NM_017554.3	c.1294A>G	p.Met432Val	missense_variant	6/17	ENST00000474629.7
PARP14	XM_011512929.3	c.1294A>G	p.Met432Val	missense_variant	6/10
PARP14	XR_007095695.1	n.1339A>G		non_coding_transcript_exon_variant	6/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP14	ENST00000474629.7	c.1294A>G	p.Met432Val	missense_variant	6/17	1	NM_017554.3	P1
PARP14	ENST00000460683.1	c.817A>G	p.Met273Val	missense_variant, NMD_transcript_variant	3/14	5
PARP14	ENST00000649945.1	c.836-3894A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

May 27, 2022

The c.1294A>G (p.M432V) alteration is located in exon 6 (coding exon 6) of the PARP14 gene. This alteration results from a A to G substitution at nucleotide position 1294, causing the methionine (M) at amino acid position 432 to be replaced by a valine (V). 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	0.086
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.3
Dann	Benign	0.35
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.041
Sift	Benign	1.0	T
Sift4G	Benign	0.53	T
Polyphen		0.0040	B
Vest4		0.030
MutPred		0.20		Loss of ubiquitination at K430 (P = 0.0787);
MVP		0.29
MPC		0.19
ClinPred		0.022	T
GERP RS		2.9
Varity_R		0.041
gMVP		0.30

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: chr3-122418695;