chr19-10107354-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020230.7(PPAN):​c.190-151C>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPAN NM_020230.7 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.190-151C>G		intron	N/A	NP_064615.3
	PPAN-P2RY11	NM_001040664.3		c.190-151C>G		intron	N/A	NP_001035754.1	A0A0B4J1V8
	PPAN-P2RY11	NM_001198690.2		c.190-151C>G		intron	N/A	NP_001185619.1	A0A0A6YYI3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPAN	ENST00000253107.12	TSL:1 MANE Select	c.190-151C>G		intron	N/A	ENSP00000253107.7	Q9NQ55-1
	PPAN-P2RY11	ENST00000393796.4	TSL:1	c.190-151C>G		intron	N/A	ENSP00000377385.4	A0A0B4J1V8
	PPAN-P2RY11	ENST00000428358.5	TSL:2	c.190-151C>G		intron	N/A	ENSP00000411918.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000340 AC: 2 AN: 587982 Hom.: 0 AF XY: 0.00000329 AC XY: 1 AN XY: 303610

African (AFR) AF: 0.00 AC: 0 AN: 14934

American (AMR) AF: 0.00 AC: 0 AN: 19244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14740

East Asian (EAS) AF: 0.00 AC: 0 AN: 31650

South Asian (SAS) AF: 0.0000208 AC: 1 AN: 48078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2616

European-Non Finnish (NFE) AF: 0.00000252 AC: 1 AN: 396196

Other (OTH) AF: 0.00 AC: 0 AN: 30586

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 76124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.67
DANN	Benign	0.27
PhyloP100		-1.2

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;