chr16-14436869-G-A

Variant names:

• chr16-14436869-G-A
• rs113631743
• NM_002582.4:c.1865-97C>T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -2.80
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4

  Inheritance: AD, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• dyskeratosis congenita, autosomal recessive 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• dyskeratosis congenita

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Hoyeraal-Hreidarsson syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002582.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARN	NM_002582.4	MANE Select	c.1865-97C>T		intron	N/A	NP_002573.1	O95453-1
	PARN	NM_001242992.2		c.1727-97C>T		intron	N/A	NP_001229921.1	O95453-3
	PARN	NM_001134477.3		c.1682-97C>T		intron	N/A	NP_001127949.1	O95453-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARN	ENST00000437198.7	TSL:1 MANE Select	c.1865-97C>T		intron	N/A	ENSP00000387911.2	O95453-1
	PARN	ENST00000931608.1		c.2021-97C>T		intron	N/A	ENSP00000601667.1
	PARN	ENST00000650990.1		c.1940-97C>T		intron	N/A	ENSP00000498741.1	A0A494C0W0

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

African (AFR) AF: 0.0552 AC: 1011 AN: 18304

American (AMR) AF: 0.123 AC: 3931 AN: 32040

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 5853 AN: 19508

East Asian (EAS) AF: 0.000368 AC: 12 AN: 32610

South Asian (SAS) AF: 0.141 AC: 8777 AN: 62320

European-Finnish (FIN) AF: 0.261 AC: 12235 AN: 46812

Middle Eastern (MID) AF: 0.291 AC: 1114 AN: 3830

European-Non Finnish (NFE) AF: 0.224 AC: 103215 AN: 461640

Other (OTH) AF: 0.200 AC: 7036 AN: 35228

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

African (AFR) AF: 0.0544 AC: 2259 AN: 41560

American (AMR) AF: 0.158 AC: 2424 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1078 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.129 AC: 621 AN: 4826

European-Finnish (FIN) AF: 0.271 AC: 2865 AN: 10580

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15668 AN: 67998

Other (OTH) AF: 0.201 AC: 423 AN: 2108

Alfa AF: 0.161 Hom.: 1191

Bravo AF: 0.154

Asia WGS AF: 0.0630 AC: 223 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.093
DANN	Benign	0.63
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs113631743; hg19: chr16-14530726;