chr3-122721219-A-T

Variant names:

• chr3-122721219-A-T
• rs6438759
• ENST00000474669.1:n.3801A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000474669.1(PARP14):​n.3801A>T variant causes a non coding transcript exon 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 ENST00000474669.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 3 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 -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000474669.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP14	NM_017554.3	MANE Select	c.4941+831A>T		intron	N/A	NP_060024.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP14	ENST00000474669.1	TSL:1	n.3801A>T		non_coding_transcript_exon	Exon 10 of 10
	PARP14	ENST00000474629.7	TSL:1 MANE Select	c.4941+831A>T		intron	N/A	ENSP00000418194.2
	PARP14	ENST00000460683.1	TSL:5	n.*729A>T		non_coding_transcript_exon	Exon 12 of 14	ENSP00000420649.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 494

American (AMR) AF: 0.00 AC: 0 AN: 3544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1620

East Asian (EAS) AF: 0.00 AC: 0 AN: 1350

South Asian (SAS) AF: 0.0000600 AC: 1 AN: 16674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 49632

Other (OTH) AF: 0.00 AC: 0 AN: 4082

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.69
PhyloP100		0.32

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: rs6438759; hg19: chr3-122440066;