Variant rs531994703 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_002582.4(PARN):c.840+6del variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.000718 in 1,585,782 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 3 hom. )

Consequence

PARN
NM_002582.4 splice_donor_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.42

Variant links:

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]

PARN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 16-14599897-CA-C is Benign according to our data. Variant chr16-14599897-CA-C is described in ClinVar as [Benign]. Clinvar id is 436150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-14599897-CA-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0042 (639/152232) while in subpopulation AFR AF= 0.0145 (604/41530). AF 95% confidence interval is 0.0136. There are 5 homozygotes in gnomad4. There are 304 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARN	NM_002582.4 linkuse as main transcript	c.840+6del		splice_donor_region_variant, intron_variant		ENST00000437198.7	NP_002573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARN	ENST00000437198.7 linkuse as main transcript	c.840+6del		splice_donor_region_variant, intron_variant		1	NM_002582.4	ENSP00000387911	P1	O95453-1

Frequencies

GnomAD3 genomes

AF:

0.00418

AC:

636

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00184

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000918

AC:

222

AN:

241924

Hom.:

AF XY:

0.000709

AC XY:

AN XY:

131200

show subpopulations

Gnomad AFR exome

AF:

0.0132

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.000348

AC:

499

AN:

1433550

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

209

AN XY:

714298

show subpopulations

Gnomad4 AFR exome

AF:

0.0126

Gnomad4 AMR exome

AF:

0.000607

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000458

Gnomad4 OTH exome

AF:

0.000842

GnomAD4 genome

AF:

0.00420

AC:

639

AN:

152232

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

304

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0145

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.0000493

Hom.:

Bravo

AF:

0.00444

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 28, 2019

- -

PARN-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 18, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4;C4225356:Dyskeratosis congenita, autosomal recessive 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 10, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.21

Position offset: -41

DS_DL_spliceai

0.21

Position offset: 7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over