Variant rs13021 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002687.4(PNN):c.2011A>G(p.Ser671Gly) variant causes a missense change. The variant allele was found at a frequency of 0.102 in 1,613,688 control chromosomes in the GnomAD database, including 9,954 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.094 ( 896 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9058 hom. )

Consequence

PNN
NM_002687.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.03

Variant links:

Genes affected

PNN (HGNC:9162): (pinin, desmosome associated protein) Enables RNA binding activity. Predicted to be involved in cell adhesion and mRNA splicing, via spliceosome. Predicted to act upstream of or within cell-cell adhesion. Located in nuclear speck. Part of catalytic step 2 spliceosome. Colocalizes with exon-exon junction complex. [provided by Alliance of Genome Resources, Apr 2022]

PNN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013381839).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNN	NM_002687.4 linkuse as main transcript	c.2011A>G	p.Ser671Gly	missense_variant	9/9	ENST00000216832.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNN	ENST00000216832.9 linkuse as main transcript	c.2011A>G	p.Ser671Gly	missense_variant	9/9	1	NM_002687.4	P1
PNN	ENST00000557680.1 linkuse as main transcript	n.471-589A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0942

AC:

14335

AN:

152132

Hom.:

897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0718

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0841

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.0788

Gnomad FIN

AF:

0.0516

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.0867

GnomAD3 exomes

AF:

0.106

AC:

26757

AN:

251320

Hom.:

1973

AF XY:

0.104

AC XY:

14125

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0711

Gnomad AMR exome

AF:

0.0954

Gnomad ASJ exome

AF:

0.0993

Gnomad EAS exome

AF:

0.319

Gnomad SAS exome

AF:

0.0672

Gnomad FIN exome

AF:

0.0608

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.103

AC:

150755

AN:

1461438

Hom.:

9058

Cov.:

AF XY:

0.102

AC XY:

74212

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.0700

Gnomad4 AMR exome

AF:

0.0956

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.318

Gnomad4 SAS exome

AF:

0.0672

Gnomad4 FIN exome

AF:

0.0622

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.0942

AC:

14337

AN:

152250

Hom.:

896

Cov.:

AF XY:

0.0918

AC XY:

6831

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0719

Gnomad4 AMR

AF:

0.0841

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.316

Gnomad4 SAS

AF:

0.0784

Gnomad4 FIN

AF:

0.0516

Gnomad4 NFE

AF:

0.101

Gnomad4 OTH

AF:

0.0863

Alfa

AF:

0.103

Hom.:

1607

Bravo

AF:

0.0979

TwinsUK

AF:

0.0987

AC:

366

ALSPAC

AF:

0.107

AC:

411

ESP6500AA

AF:

0.0756

AC:

333

ESP6500EA

AF:

0.109

AC:

940

ExAC

AF:

0.106

AC:

12930

Asia WGS

AF:

0.165

AC:

570

AN:

3478

EpiCase

AF:

0.105

EpiControl

AF:

0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0013

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.46

MutationTaster

Benign

0.018

PrimateAI

Benign

0.43

PROVEAN

Benign

0.26

REVEL

Benign

0.12

Sift

Uncertain

0.017

Sift4G

Uncertain

0.023

Polyphen

0.92

Vest4

0.053

MPC

0.064

ClinPred

0.046

GERP RS

4.7

Varity_R

0.18

gMVP

0.057

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over