Variant 3-122681040-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017554.3(PARP14):c.157C>G(p.Arg53Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PARP14
NM_017554.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.46

Variant links:

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]

PARP14 links:

PARP14 (HGNC:):

PARP14 links:

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ACMG classification

Classification made for transcript

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=0.18732196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP14	NM_017554.3 linkuse as main transcript	c.157C>G	p.Arg53Gly	missense_variant	1/17	ENST00000474629.7	NP_060024.2	Q460N5-6Q8N546
PARP14	XM_011512929.3 linkuse as main transcript	c.157C>G	p.Arg53Gly	missense_variant	1/10		XP_011511231.1
PARP14	XR_007095695.1 linkuse as main transcript	n.202C>G		non_coding_transcript_exon_variant	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PARP14	ENST00000474629.7 linkuse as main transcript	c.157C>G	p.Arg53Gly	missense_variant	1/17	1	NM_017554.3	ENSP00000418194.2	Q460N5-6
PARP14	ENST00000494811.2 linkuse as main transcript	c.157C>G	p.Arg53Gly	missense_variant	1/4	4		ENSP00000418535.2	H7C4Y3
PARP14	ENST00000649945.1 linkuse as main transcript	n.157C>G		non_coding_transcript_exon_variant	1/16			ENSP00000497854.1	A0A3B3ITD5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000808

AC:

AN:

247658

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134710

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000893

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461380

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2024

The c.157C>G (p.R53G) alteration is located in exon 1 (coding exon 1) of the PARP14 gene. This alteration results from a C to G substitution at nucleotide position 157, causing the arginine (R) at amino acid position 53 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

0.19

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.5

D;.

REVEL

Benign

0.089

Sift

Uncertain

0.017

D;.

Sift4G

Uncertain

0.026

D;.

Polyphen

1.0

D;.

Vest4

0.22

MutPred

0.38

Loss of stability (P = 0.0254);Loss of stability (P = 0.0254);

MVP

0.42

MPC

2.4

ClinPred

0.61

GERP RS

-0.52

Varity_R

0.16

gMVP

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over