3-122699779-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2 PP2 BP4_Strong BP6_Moderate

The NM_017554.3(PARP14):c.1225A>G(p.Met409Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PARP14 NM_017554.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.61

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 Likely_benign. Variant got -3 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=0.045504063).
• BP6: Variant 3-122699779-A-G is Benign according to our data. Variant chr3-122699779-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2297946.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP14	NM_017554.3	c.1225A>G	p.Met409Val	missense_variant	6/17	ENST00000474629.7
PARP14	XM_011512929.3	c.1225A>G	p.Met409Val	missense_variant	6/10
PARP14	XR_007095695.1	n.1270A>G		non_coding_transcript_exon_variant	6/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP14	ENST00000474629.7	c.1225A>G	p.Met409Val	missense_variant	6/17	1	NM_017554.3	P1
PARP14	ENST00000460683.1	c.748A>G	p.Met250Val	missense_variant, NMD_transcript_variant	3/14	5
PARP14	ENST00000649945.1	c.836-3963A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	9.5
Dann	Benign	0.23
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-2.8	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.19		Loss of catalytic residue at V405 (P = 0.0497);
MVP		0.27
MPC		0.19
ClinPred		0.036	T
GERP RS		1.3
Varity_R		0.029
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-122418626;