chr3-122685286-G-T

Variant names:

• chr3-122685286-G-T
• rs749044110
• NM_017554.3:c.289G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017554.3(PARP14):​c.289G>T​(p.Asp97Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. D97N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: PARP14 NM_017554.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05344197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP14	NM_017554.3	c.289G>T	p.Asp97Tyr	missense_variant	Exon 2 of 17	ENST00000474629.7	NP_060024.2
PARP14	XM_011512929.3	c.289G>T	p.Asp97Tyr	missense_variant	Exon 2 of 10		XP_011511231.1
PARP14	XR_007095695.1	n.334G>T		non_coding_transcript_exon_variant	Exon 2 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP14	ENST00000474629.7	c.289G>T	p.Asp97Tyr	missense_variant	Exon 2 of 17	1	NM_017554.3	ENSP00000418194.2
PARP14	ENST00000494811.2	c.289G>T	p.Asp97Tyr	missense_variant	Exon 2 of 4	4		ENSP00000418535.2
PARP14	ENST00000649945.1	n.289G>T		non_coding_transcript_exon_variant	Exon 2 of 16			ENSP00000497854.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1461532 Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19 AN XY: 727046

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000781 AC: 31 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111794

Other (OTH) AF: 0.0000166 AC: 1 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.36
DEOGEN2	Benign	0.0030	T;.
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.31	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PhyloP100		-1.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.30	N;.
REVEL	Benign	0.037
Sift	Benign	1.0	T;.
Sift4G	Uncertain	0.030	D;.
Polyphen		0.11	B;.
Vest4		0.10
MutPred		0.29		Loss of disorder (P = 0.0155);Loss of disorder (P = 0.0155);
MVP		0.40
MPC		0.25
ClinPred		0.054	T
GERP RS		3.0
Varity_R		0.029
gMVP		0.35
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs749044110; hg19: chr3-122404133; COSMIC: COSV72111704; COSMIC: COSV72111704;