rs780601730

Variant names:

• chr3-122692333-C-A
• rs780601730
• NM_017554.3:c.388C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-122692333-C-A
• chr3-122692333-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017554.3(PARP14):​c.388C>A​(p.Leu130Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. L130F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PARP14 NM_017554.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.627
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07387358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP14	NM_017554.3	c.388C>A	p.Leu130Ile	missense_variant	Exon 4 of 17	ENST00000474629.7	NP_060024.2
PARP14	XM_011512929.3	c.388C>A	p.Leu130Ile	missense_variant	Exon 4 of 10		XP_011511231.1
PARP14	XR_007095695.1	n.433C>A		non_coding_transcript_exon_variant	Exon 4 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP14	ENST00000474629.7	c.388C>A	p.Leu130Ile	missense_variant	Exon 4 of 17	1	NM_017554.3	ENSP00000418194.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460424 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726506

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110830

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.9
DANN	Benign	0.24
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.63
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.050
Sift	Benign	0.48	T
Sift4G	Benign	0.39	T
Polyphen		0.29	B
Vest4		0.12
MutPred		0.16		Gain of methylation at K127 (P = 0.0402);
MVP		0.34
MPC		0.25
ClinPred		0.15	T
GERP RS		4.2
Varity_R		0.052
gMVP		0.096
Mutation Taster		=94/6	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: rs780601730; hg19: chr3-122411180;