rs11666402

Positions:

• chr19-10108400-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020230.7(PPAN):​c.513+266T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,930 control chromosomes in the GnomAD database, including 12,207 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.

• Frequency: Genomes: 𝑓 0.39 (12207 hom., cov: 31)
• Consequence: PPAN NM_020230.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494

Genes affected

PPAN (HGNC:9227): (peter pan homolog) The protein encoded by this gene is an evolutionarily conserved protein similar to yeast SSF1 as well as to the gene product of the Drosophila gene peter pan (ppan). SSF1 is known to be involved in the second step of mRNA splicing. Both SSF1 and ppan are essential for cell growth and proliferation. Exogenous expression of this gene was reported to reduce the anchorage-independent growth of some tumor cells. Read-through transcription of this gene with P2RY11/P2Y(11), an adjacent downstream gene that encodes an ATP receptor, has been found. These read-through transcripts are ubiquitously present and up-regulated during granulocyte differentiation. [provided by RefSeq, Nov 2010]

PPAN-P2RY11 (HGNC:33526): (PPAN-P2RY11 readthrough) This locus represents naturally occurring read-through transcription between the adjacent PPAN and P2RY11 genes. Alternative splicing results in two transcript variants, one of which encodes a fusion protein that shares sequence identity with each individual gene product. This transcript is found to be ubiquitously expressed and is up-regulated by agents inducing granulocytic differentiation. However, its functional significance in vivo remains unclear. [provided by RefSeq, Nov 2010]

PPAN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPAN	NM_020230.7	c.513+266T>C		intron_variant		ENST00000253107.12	NP_064615.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPAN	ENST00000253107.12	c.513+266T>C		intron_variant		1	NM_020230.7	ENSP00000253107.7
PPAN-P2RY11	ENST00000393796.4	c.513+266T>C		intron_variant		1		ENSP00000377385.4

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58753 AN: 151812 Hom.: 12205 Cov.: 31

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.444

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.387 AC: 58785 AN: 151930 Hom.: 12207 Cov.: 31 AF XY: 0.388 AC XY: 28819 AN XY: 74266

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.445

Alfa AF: 0.442 Hom.: 27785

Bravo AF: 0.383

Asia WGS AF: 0.407 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11666402; hg19: chr19-10219076;