Variant 3-122692438-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017554.3(PARP14):c.493C>G(p.Leu165Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PARP14
NM_017554.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.72

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP14	NM_017554.3 linkuse as main transcript	c.493C>G	p.Leu165Val	missense_variant	4/17	ENST00000474629.7	NP_060024.2	Q460N5-6Q8N546
PARP14	XM_011512929.3 linkuse as main transcript	c.493C>G	p.Leu165Val	missense_variant	4/10		XP_011511231.1
PARP14	XR_007095695.1 linkuse as main transcript	n.538C>G		non_coding_transcript_exon_variant	4/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PARP14	ENST00000474629.7 linkuse as main transcript	c.493C>G	p.Leu165Val	missense_variant	4/17	1	NM_017554.3	ENSP00000418194.2	Q460N5-6
PARP14	ENST00000494811.2 linkuse as main transcript	c.356-2988C>G		intron_variant		4		ENSP00000418535.2	H7C4Y3
PARP14	ENST00000460683.1 linkuse as main transcript	n.16C>G		non_coding_transcript_exon_variant	1/14	5		ENSP00000420649.1	H7C5R8
PARP14	ENST00000649945.1 linkuse as main transcript	n.493C>G		non_coding_transcript_exon_variant	4/16			ENSP00000497854.1	A0A3B3ITD5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249024

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135080

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461292

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

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

Dec 16, 2023

The c.493C>G (p.L165V) 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 493, causing the leucine (L) at amino acid position 165 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

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.8

DANN

Benign

0.90

DEOGEN2

Benign

0.034

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.74

M_CAP

Benign

0.044

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.0

REVEL

Benign

0.21

Sift

Uncertain

0.014

Sift4G

Uncertain

0.0050

Polyphen

0.91

Vest4

0.29

MutPred

0.27

Gain of sheet (P = 0.0149);

MVP

0.61

MPC

0.38

ClinPred

0.11

GERP RS

-3.1

Varity_R

0.068

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.21

Position offset: -1

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