3-122721219-A-T

Position:

• chr3-122721219-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017554.3(PARP14):​c.4941+831A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 81,850 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.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: PARP14 NM_017554.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP14	NM_017554.3	c.4941+831A>T		intron_variant		ENST00000474629.7	NP_060024.2
PARP14	XR_007095695.1	n.5118A>T		non_coding_transcript_exon_variant	16/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP14	ENST00000474629.7	c.4941+831A>T		intron_variant		1	NM_017554.3	ENSP00000418194	P1
PARP14	ENST00000474669.1	n.3801A>T		non_coding_transcript_exon_variant	10/10	1
PARP14	ENST00000460683.1	c.*729A>T		3_prime_UTR_variant, NMD_transcript_variant	12/14	5		ENSP00000420649
PARP14	ENST00000649945.1	c.*1816+831A>T		intron_variant, NMD_transcript_variant				ENSP00000497854

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000122 AC: 1 AN: 81850 Hom.: 0 Cov.: 0 AF XY: 0.0000224 AC XY: 1 AN XY: 44596

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000600

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs6438759; hg19: chr3-122440066;