16-14436763-G-C

Variant names:

• chr16-14436763-G-C
• rs201963032
• NM_002582.4:c.1874C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002582.4(PARN):​c.1874C>G​(p.Ser625Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,439,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PARN NM_002582.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08150482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARN	NM_002582.4	c.1874C>G	p.Ser625Trp	missense_variant	Exon 24 of 24	ENST00000437198.7	NP_002573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARN	ENST00000437198.7	c.1874C>G	p.Ser625Trp	missense_variant	Exon 24 of 24	1	NM_002582.4	ENSP00000387911.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000955 AC: 2 AN: 209510 Hom.: 0 AF XY: 0.00000889 AC XY: 1 AN XY: 112488

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000337

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: 0.00

Gnomad OTH exome AF: 0.000184

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1439114 Hom.: 0 Cov.: 29 AF XY: 0.00000140 AC XY: 1 AN XY: 713464

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000490

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T;.;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.73	T;T;T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.082	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.85	N;N;N;N
REVEL	Benign	0.038
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		0.77	P;.;.;.
Vest4		0.34
MutPred		0.27		Loss of disorder (P = 0.0127);.;.;.;
MVP		0.26
MPC		0.39
ClinPred		0.33	T
GERP RS		2.4
Varity_R		0.084
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs201963032; hg19: chr16-14530620;