10-70212594-C-T

Variant names:

• chr10-70212594-C-T
• rs12570967
• NM_021129.4:c.511+869G>A

Variant summary

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

The NM_021129.4(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 NM_021129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021129.4. 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
	PPA1	NM_021129.4	MANE Select	c.511+869G>A		intron	N/A	NP_066952.1	Q15181

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPA1	ENST00000373232.8	TSL:1 MANE Select	c.511+869G>A		intron	N/A	ENSP00000362329.2	Q15181
	PPA1	ENST00000851537.1		c.457+869G>A		intron	N/A	ENSP00000521596.1
	PPA1	ENST00000851538.1		c.424+869G>A		intron	N/A	ENSP00000521597.1

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

African (AFR) AF: 0.0150 AC: 622 AN: 41488

American (AMR) AF: 0.115 AC: 1760 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3470

East Asian (EAS) AF: 0.218 AC: 1126 AN: 5168

South Asian (SAS) AF: 0.0966 AC: 465 AN: 4814

European-Finnish (FIN) AF: 0.0356 AC: 376 AN: 10566

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0494 AC: 3356 AN: 67978

Other (OTH) AF: 0.0711 AC: 150 AN: 2110

Alfa AF: 0.0475 Hom.: 37

Bravo AF: 0.0591

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.65
PhyloP100		1.4
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: rs12570967; hg19: chr10-71972350;