NM_020230.7:c.513+266T>C

Variant names:

• chr19-10108400-T-C
• rs11666402
• NM_020230.7:c.513+266T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPAN	NM_020230.7	c.513+266T>C		intron_variant	Intron 5 of 11	ENST00000253107.12	NP_064615.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPAN	ENST00000253107.12	c.513+266T>C		intron_variant	Intron 5 of 11	1	NM_020230.7	ENSP00000253107.7
PPAN-P2RY11	ENST00000393796.4	c.513+266T>C		intron_variant	Intron 5 of 12	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

African (AFR) AF: 0.231 AC: 9583 AN: 41428

American (AMR) AF: 0.470 AC: 7167 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1513 AN: 3464

East Asian (EAS) AF: 0.356 AC: 1835 AN: 5158

South Asian (SAS) AF: 0.463 AC: 2228 AN: 4814

European-Finnish (FIN) AF: 0.455 AC: 4795 AN: 10548

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.445 AC: 30218 AN: 67950

Other (OTH) AF: 0.445 AC: 940 AN: 2112

Alfa AF: 0.430 Hom.: 56773

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
PhyloP100		-0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs11666402; hg19: chr19-10219076;