3-122699590-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_017554.3(PARP14):c.1036G>A(p.Asp346Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,613,744 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

PARP14
NM_017554.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0520

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.038754165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PARP14	NM_017554.3 linkuse as main transcript	c.1036G>A	p.Asp346Asn	missense_variant	6/17	ENST00000474629.7
PARP14	XM_011512929.3 linkuse as main transcript	c.1036G>A	p.Asp346Asn	missense_variant	6/10
PARP14	XR_007095695.1 linkuse as main transcript	n.1081G>A		non_coding_transcript_exon_variant	6/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP14	ENST00000474629.7 linkuse as main transcript	c.1036G>A	p.Asp346Asn	missense_variant	6/17	1	NM_017554.3	P1	Q460N5-6
PARP14	ENST00000460683.1 linkuse as main transcript	c.559G>A	p.Asp187Asn	missense_variant, NMD_transcript_variant	3/14	5
PARP14	ENST00000649945.1 linkuse as main transcript	c.835+3928G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

249188

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135182

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

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:

0.0000531

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000125

AC:

183

AN:

1461542

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

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:

0.000150

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000151

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000212

Hom.:

Bravo

AF:

0.000136

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000505

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

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

Sep 15, 2021

The c.1036G>A (p.D346N) alteration is located in exon 6 (coding exon 6) of the PARP14 gene. This alteration results from a G to A substitution at nucleotide position 1036, causing the aspartic acid (D) at amino acid position 346 to be replaced by an asparagine (N). 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

0.075

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.61

M_CAP

Benign

0.024

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.8

REVEL

Benign

0.090

Sift

Benign

0.36

Sift4G

Benign

0.45

Polyphen

0.014

Vest4

0.11

MVP

0.33

MPC

0.19

ClinPred

0.033

GERP RS

-1.1

Varity_R

0.041

gMVP

0.37

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