16-14436869-G-A

Position:

• chr16-14436869-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002582.4(PARN):​c.1865-97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 864,516 control chromosomes in the GnomAD database, including 18,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2652 hom., cov: 32)
  • Exomes 𝑓: 0.20 (16043 hom.)
• Consequence: PARN NM_002582.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.80

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-14436869-G-A is Benign according to our data. Variant chr16-14436869-G-A is described in ClinVar as [Benign]. Clinvar id is 1178066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARN	NM_002582.4	c.1865-97C>T		intron_variant		ENST00000437198.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARN	ENST00000437198.7	c.1865-97C>T		intron_variant		1	NM_002582.4	P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25590 AN: 152108 Hom.: 2654 Cov.: 32

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.201 AC: 143184 AN: 712292 Hom.: 16043 AF XY: 0.199 AC XY: 74511 AN XY: 373666

Gnomad4 AFR exome AF: 0.0552

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.000368

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.168 AC: 25582 AN: 152224 Hom.: 2652 Cov.: 32 AF XY: 0.169 AC XY: 12596 AN XY: 74422

Gnomad4 AFR AF: 0.0544

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.201

Alfa AF: 0.203 Hom.: 732

Bravo AF: 0.154

Asia WGS AF: 0.0630 AC: 223 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.093
DANN	Benign	0.63

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: rs113631743; hg19: chr16-14530726;