chr3-122680906-C-A

Variant names:

• chr3-122680906-C-A
• rs536654763
• NM_017554.3:c.23C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017554.3(PARP14):​c.23C>A​(p.Pro8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P8L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PARP14 NM_017554.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26848146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP14	NM_017554.3	c.23C>A	p.Pro8Gln	missense_variant	Exon 1 of 17	ENST00000474629.7	NP_060024.2
PARP14	XM_011512929.3	c.23C>A	p.Pro8Gln	missense_variant	Exon 1 of 10		XP_011511231.1
PARP14	XR_007095695.1	n.68C>A		non_coding_transcript_exon_variant	Exon 1 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP14	ENST00000474629.7	c.23C>A	p.Pro8Gln	missense_variant	Exon 1 of 17	1	NM_017554.3	ENSP00000418194.2
PARP14	ENST00000494811.2	c.23C>A	p.Pro8Gln	missense_variant	Exon 1 of 4	4		ENSP00000418535.2
PARP14	ENST00000649945.1	n.23C>A		non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000497854.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457956 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 724990

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39524

South Asian (SAS) AF: 0.00 AC: 0 AN: 85538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110404

Other (OTH) AF: 0.00 AC: 0 AN: 60124

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;.
PhyloP100		2.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.7	D;.
REVEL	Benign	0.20
Sift	Benign	0.091	T;.
Sift4G	Benign	0.11	T;.
Polyphen		1.0	D;.
Vest4		0.44
MutPred		0.49		Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);
MVP		0.58
MPC		2.6
ClinPred		1.0	D
GERP RS		3.5
PromoterAI		-0.067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.10
gMVP		0.72
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs536654763; hg19: chr3-122399753;