19-10111142-C-A

Variant names:

• chr19-10111142-C-A
• rs780194176
• NM_020230.7:c.1399C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020230.7(PPAN):​c.1399C>A​(p.Arg467Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R467C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PPAN NM_020230.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.087699324).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020230.7. 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
	PPAN	NM_020230.7	MANE Select	c.1399C>A	p.Arg467Ser	missense	Exon 12 of 12	NP_064615.3
	PPAN	NM_001346139.1		c.1396C>A	p.Arg466Ser	missense	Exon 12 of 12	NP_001333068.1
	PPAN	NM_001346141.1		c.1240C>A	p.Arg414Ser	missense	Exon 11 of 11	NP_001333070.1	A8MV53

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPAN	ENST00000253107.12	TSL:1 MANE Select	c.1399C>A	p.Arg467Ser	missense	Exon 12 of 12	ENSP00000253107.7	Q9NQ55-1
	PPAN-P2RY11	ENST00000393796.4	TSL:1	c.1279+120C>A		intron	N/A	ENSP00000377385.4	A0A0B4J1V8
	PPAN	ENST00000891444.1		c.1396C>A	p.Arg466Ser	missense	Exon 12 of 12	ENSP00000561503.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.7
DANN	Benign	0.86
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.41
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.082
Sift	Benign	0.073	T
Sift4G	Benign	0.15	T
Polyphen		0.69	P
Vest4		0.23
MutPred		0.34		Gain of phosphorylation at R467 (P = 6e-04)
MVP		0.014
ClinPred		0.13	T
GERP RS		0.44
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4
Varity_R		0.16
gMVP		0.27
Mutation Taster		=100/0	polymorphism

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: rs780194176; hg19: chr19-10221818;