19-10107354-C-T

Variant names:

• chr19-10107354-C-T
• rs1551570
• NM_020230.7:c.190-151C>T

Variant summary

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

The NM_020230.7(PPAN):​c.190-151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 738,918 control chromosomes in the GnomAD database, including 129,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.60 (27299 hom., cov: 33)
  • Exomes 𝑓: 0.58 (101713 hom.)
• Consequence: PPAN NM_020230.7 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.21
• Publications: 29 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPAN	NM_020230.7	c.190-151C>T		intron_variant	Intron 2 of 11	ENST00000253107.12	NP_064615.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPAN	ENST00000253107.12	c.190-151C>T		intron_variant	Intron 2 of 11	1	NM_020230.7	ENSP00000253107.7
PPAN-P2RY11	ENST00000393796.4	c.190-151C>T		intron_variant	Intron 2 of 12	1		ENSP00000377385.4

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90484 AN: 151972 Hom.: 27266 Cov.: 33

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.619

GnomAD4 exome AF: 0.585 AC: 343106 AN: 586826 Hom.: 101713 AF XY: 0.589 AC XY: 178518 AN XY: 303072

African (AFR) AF: 0.597 AC: 8910 AN: 14914

American (AMR) AF: 0.684 AC: 13142 AN: 19224

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 8125 AN: 14718

East Asian (EAS) AF: 0.715 AC: 22620 AN: 31632

South Asian (SAS) AF: 0.677 AC: 32544 AN: 48042

European-Finnish (FIN) AF: 0.592 AC: 17687 AN: 29894

Middle Eastern (MID) AF: 0.516 AC: 1342 AN: 2602

European-Non Finnish (NFE) AF: 0.558 AC: 220737 AN: 395288

Other (OTH) AF: 0.590 AC: 17999 AN: 30512

GnomAD4 genome AF: 0.596 AC: 90577 AN: 152092 Hom.: 27299 Cov.: 33 AF XY: 0.601 AC XY: 44659 AN XY: 74336

African (AFR) AF: 0.608 AC: 25218 AN: 41468

American (AMR) AF: 0.654 AC: 10003 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1942 AN: 3472

East Asian (EAS) AF: 0.725 AC: 3759 AN: 5184

South Asian (SAS) AF: 0.691 AC: 3335 AN: 4824

European-Finnish (FIN) AF: 0.604 AC: 6384 AN: 10570

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 38006 AN: 67968

Other (OTH) AF: 0.620 AC: 1307 AN: 2108

Alfa AF: 0.573 Hom.: 76124

Bravo AF: 0.602

Asia WGS AF: 0.691 AC: 2403 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Cataplexy and narcolepsy Other:1

Dec 10, 2014

Center for Narcolepsy, Stanford University

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.56
PhyloP100		-1.2
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: rs1551570; hg19: chr19-10218030; COSMIC: COSV53455105; COSMIC: COSV53455105;