rs17260976

chr16-14585170-C-Gchr16-14585170-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002582.4(PARN):c.963-379G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,174 control chromosomes in the GnomAD database, including 1,341 homozygotes. 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: 𝑓 0.12 (1341 hom., cov: 32)
• Consequence: PARN NM_002582.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

Genes affected

PARN (HGNC:8609): (poly(A)-specific ribonuclease) The protein encoded by this gene is a 3'-exoribonuclease, with similarity to the RNase D family of 3'-exonucleases. It prefers poly(A) as the substrate, hence, efficiently degrades poly(A) tails of mRNAs. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs. This protein is also involved in silencing of certain maternal mRNAs during oocyte maturation and early embryonic development, as well as in nonsense-mediated decay (NMD) of mRNAs that contain premature stop codons. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARN	NM_002582.4	c.963-379G>C		intron_variant		ENST00000437198.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARN	ENST00000437198.7	c.963-379G>C		intron_variant		1	NM_002582.4	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18239 AN: 152056 Hom.: 1341 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.131

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.120 AC: 18237 AN: 152174 Hom.: 1341 Cov.: 32 AF XY: 0.113 AC XY: 8435 AN XY: 74398

Gnomad4 AFR AF: 0.0585

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0432

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.130

Alfa AF: 0.144 Hom.: 209

Bravo AF: 0.118

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.55
Dann	Benign	0.40

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: rs17260976; hg19: chr16-14679027;