10-70212594-C-T

Position:

• chr10-70212594-C-T

Variant summary

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

The ENST00000373232.8(PPA1):​c.511+869G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0542 in 152,080 control chromosomes in the GnomAD database, including 375 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 0.054 (375 hom., cov: 33)
• Consequence: PPA1 ENST00000373232.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

PPA1 (HGNC:9226): (inorganic pyrophosphatase 1) The protein encoded by this gene is a member of the inorganic pyrophosphatase (PPase) family. PPases catalyze the hydrolysis of pyrophosphate to inorganic phosphate, which is important for the phosphate metabolism of cells. Studies of a similar protein in bovine suggested a cytoplasmic localization of this enzyme. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPA1	NM_021129.4	c.511+869G>A		intron_variant		ENST00000373232.8	NP_066952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPA1	ENST00000373232.8	c.511+869G>A		intron_variant		1	NM_021129.4	ENSP00000362329	P1
PPA1	ENST00000625364.1	c.511+869G>A		intron_variant		5		ENSP00000486162
PPA1	ENST00000373230.7	c.511+869G>A		intron_variant, NMD_transcript_variant		5		ENSP00000362327

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 8240 AN: 151962 Hom.: 374 Cov.: 33

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.0963

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0494

Gnomad OTH AF: 0.0694

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

GnomAD4 genome AF: 0.0542 AC: 8247 AN: 152080 Hom.: 375 Cov.: 33 AF XY: 0.0568 AC XY: 4225 AN XY: 74348

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.0966

Gnomad4 FIN AF: 0.0356

Gnomad4 NFE AF: 0.0494

Gnomad4 OTH AF: 0.0711

Alfa AF: 0.0470 Hom.: 35

Bravo AF: 0.0591

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.65
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: rs12570967; hg19: chr10-71972350;