rs13021

Variant names:

• chr14-39181720-A-G
• rs13021
• NM_002687.4:c.2011A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-39181720-A-G
• chr14-39181720-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 12/21 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: 𝑓 0.094 (896 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9058 hom.)
• Consequence: PNN NM_002687.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.03
• Publications: 37 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002687.4. 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
	PNN	NM_002687.4	MANE Select	c.2011A>G	p.Ser671Gly	missense	Exon 9 of 9	NP_002678.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNN	ENST00000216832.9	TSL:1 MANE Select	c.2011A>G	p.Ser671Gly	missense	Exon 9 of 9	ENSP00000216832.4	Q9H307
	PNN	ENST00000911271.1		c.2011A>G	p.Ser671Gly	missense	Exon 9 of 9	ENSP00000581330.1
	PNN	ENST00000911270.1		c.2005A>G	p.Ser669Gly	missense	Exon 9 of 9	ENSP00000581329.1

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14335 AN: 152132 Hom.: 897 Cov.: 32

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

GnomAD2 exomes AF: 0.106 AC: 26757 AN: 251320 AF XY: 0.104

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 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.: 33 AF XY: 0.102 AC XY: 74212 AN XY: 727046

African (AFR) AF: 0.0700 AC: 2342 AN: 33478

American (AMR) AF: 0.0956 AC: 4276 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2653 AN: 26128

East Asian (EAS) AF: 0.318 AC: 12623 AN: 39698

South Asian (SAS) AF: 0.0672 AC: 5799 AN: 86248

European-Finnish (FIN) AF: 0.0622 AC: 3323 AN: 53408

Middle Eastern (MID) AF: 0.118 AC: 678 AN: 5766

European-Non Finnish (NFE) AF: 0.101 AC: 112588 AN: 1111608

Other (OTH) AF: 0.107 AC: 6473 AN: 60380

GnomAD4 genome AF: 0.0942 AC: 14337 AN: 152250 Hom.: 896 Cov.: 32 AF XY: 0.0918 AC XY: 6831 AN XY: 74442

African (AFR) AF: 0.0719 AC: 2986 AN: 41556

American (AMR) AF: 0.0841 AC: 1286 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 366 AN: 3470

East Asian (EAS) AF: 0.316 AC: 1638 AN: 5176

South Asian (SAS) AF: 0.0784 AC: 378 AN: 4820

European-Finnish (FIN) AF: 0.0516 AC: 548 AN: 10614

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6899 AN: 68000

Other (OTH) AF: 0.0863 AC: 182 AN: 2110

Alfa AF: 0.104 Hom.: 3328

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.46	N
PhyloP100		5.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.12
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.023	D
Polyphen		0.92	P
Vest4		0.053
MPC		0.064
ClinPred		0.046	T
GERP RS		4.7
Varity_R		0.18
gMVP		0.057
Mutation Taster		=91/9	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: rs13021; hg19: chr14-39650924; COSMIC: COSV53765466; COSMIC: COSV53765466;