rs13021

chr14-39181720-A-Gchr14-39181720-A-T

Variant summary

Our verdict is Benign. Variant got -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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.03

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

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	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	c.2011A>G	p.Ser671Gly	missense_variant	9/9	1	NM_002687.4	P1
PNN	ENST00000557680.1	n.471-589A>G		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.106 AC: 26757 AN: 251320 Hom.: 1973 AF XY: 0.104 AC XY: 14125 AN XY: 135868

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

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.: 32 AF XY: 0.0918 AC XY: 6831 AN XY: 74442

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	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
MutationTaster	Benign	0.018	P
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

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

Other links and lift over

dbSNP: rs13021; hg19: chr14-39650924; COSMIC: COSV53765466; COSMIC: COSV53765466;