3-122699437-C-T

Position:

• chr3-122699437-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017554.3(PARP14):​c.883C>T​(p.Leu295Phe) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PARP14 NM_017554.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33673248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP14	NM_017554.3	c.883C>T	p.Leu295Phe	missense_variant	6/17	ENST00000474629.7	NP_060024.2
PARP14	XM_011512929.3	c.883C>T	p.Leu295Phe	missense_variant	6/10		XP_011511231.1
PARP14	XR_007095695.1	n.928C>T		non_coding_transcript_exon_variant	6/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP14	ENST00000474629.7	c.883C>T	p.Leu295Phe	missense_variant	6/17	1	NM_017554.3	ENSP00000418194.2
PARP14	ENST00000460683.1	n.406C>T		non_coding_transcript_exon_variant	3/14	5		ENSP00000420649.1
PARP14	ENST00000649945.1	n.835+3775C>T		intron_variant				ENSP00000497854.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 26, 2024

The c.883C>T (p.L295F) alteration is located in exon 6 (coding exon 6) of the PARP14 gene. This alteration results from a C to T substitution at nucleotide position 883, causing the leucine (L) at amino acid position 295 to be replaced by a phenylalanine (F). 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	Uncertain	0.38
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.29
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.29		Loss of catalytic residue at L295 (P = 0.0646);
MVP		0.83
MPC		0.79
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.18
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr3-122418284;