3-122700016-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2 BP4_Strong BP6_Moderate BS1 BS2

The NM_017554.3(PARP14):c.1462G>A(p.Asp488Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,613,868 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (27 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (26 hom.)
• Consequence: PARP14 NM_017554.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.220

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 Benign. Variant got -13 ACMG points.

• PP2: Missense variant where missense usually causes diseases, PARP14
• BP4: Computational evidence support a benign effect (MetaRNN=0.0024738014).
• BP6: Variant 3-122700016-G-A is Benign according to our data. Variant chr3-122700016-G-A is described in ClinVar as [Benign]. Clinvar id is 780407.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1787/152278) while in subpopulation AFR AF= 0.0399 (1657/41558). AF 95% confidence interval is 0.0383. There are 27 homozygotes in gnomad4. There are 822 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP14	NM_017554.3	c.1462G>A	p.Asp488Asn	missense_variant	6/17	ENST00000474629.7
PARP14	XM_011512929.3	c.1462G>A	p.Asp488Asn	missense_variant	6/10
PARP14	XR_007095695.1	n.1507G>A		non_coding_transcript_exon_variant	6/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP14	ENST00000474629.7	c.1462G>A	p.Asp488Asn	missense_variant	6/17	1	NM_017554.3	P1
PARP14	ENST00000460683.1	c.985G>A	p.Asp329Asn	missense_variant, NMD_transcript_variant	3/14	5
PARP14	ENST00000649945.1	c.836-3726G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1784 AN: 152160 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.00308 AC: 768 AN: 248948 Hom.: 10 AF XY: 0.00247 AC XY: 333 AN XY: 135072

Gnomad AFR exome AF: 0.0381

Gnomad AMR exome AF: 0.00348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.000371

Gnomad NFE exome AF: 0.000301

Gnomad OTH exome AF: 0.00232

GnomAD4 exome AF: 0.00125 AC: 1834 AN: 1461590 Hom.: 26 Cov.: 34 AF XY: 0.00109 AC XY: 795 AN XY: 727078

Gnomad4 AFR exome AF: 0.0374

Gnomad4 AMR exome AF: 0.00358

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.000393

Gnomad4 NFE exome AF: 0.000161

Gnomad4 OTH exome AF: 0.00300

GnomAD4 genome AF: 0.0117 AC: 1787 AN: 152278 Hom.: 27 Cov.: 33 AF XY: 0.0110 AC XY: 822 AN XY: 74462

Gnomad4 AFR AF: 0.0399

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00376 Hom.: 8

Bravo AF: 0.0126

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0349 AC: 130

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.00359 AC: 434

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	9.3
Dann	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.067
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.17	B
Vest4		0.11
MVP		0.42
MPC		0.21
ClinPred		0.018	T
GERP RS		3.1
Varity_R		0.037
gMVP		0.19

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

Other links and lift over

dbSNP: rs16833413; hg19: chr3-122418863;