Genetic Variant PARP6:p.Val205Ile (chr15-72260621-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001323532.2(PARP6):c.613G>A(p.Val205Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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

PARP6
NM_001323532.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46

Variant links:

Genes affected

PARP6 (HGNC:26921): (poly(ADP-ribose) polymerase family member 6) Enables protein ADP-ribosylase activity. Involved in protein auto-ADP-ribosylation and protein mono-ADP-ribosylation. [provided by Alliance of Genome Resources, Apr 2022]

PARP6 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=0.22772932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP6	NM_001323532.2 link	c.613G>A	p.Val205Ile	missense_variant	Exon 10 of 24	ENST00000569795.6	NP_001310461.1	Q2NL67-1A0A024R5Z4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP6	ENST00000569795.6 link	c.613G>A	p.Val205Ile	missense_variant	Exon 10 of 24	5	NM_001323532.2	ENSP00000456348.1		Q2NL67-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.613G>A (p.V205I) alteration is located in exon 9 (coding exon 8) of the PARP6 gene. This alteration results from a G to A substitution at nucleotide position 613, causing the valine (V) at amino acid position 205 to be replaced by an isoleucine (I). 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

0.080

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;.;.;T;.

Eigen

Benign

-0.053

Eigen_PC

Benign

0.069

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

.;D;D;D;D

M_CAP

Benign

0.0067

MetaRNN

Benign

0.23

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.69

N;.;N;N;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.16

N;.;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.17

T;.;T;T;T

Sift4G

Benign

0.45

T;T;T;T;T

Polyphen

0.32

B;.;.;B;.

Vest4

0.43

MutPred

0.19

Loss of methylation at R204 (P = 0.0536);Loss of methylation at R204 (P = 0.0536);Loss of methylation at R204 (P = 0.0536);Loss of methylation at R204 (P = 0.0536);Loss of methylation at R204 (P = 0.0536);

MVP

0.15

MPC

0.31

ClinPred

0.65

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.057

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over