4-105369643-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_176869.3(PPA2):c.*82T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,103,820 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (21 hom.)
• Consequence: PPA2 NM_176869.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.730

Genes affected

PPA2 (HGNC:28883): (inorganic pyrophosphatase 2) The protein encoded by this gene is localized to the mitochondrion, is highly similar to members of the inorganic pyrophosphatase (PPase) family, and contains the signature sequence essential for the catalytic activity of PPase. PPases catalyze the hydrolysis of pyrophosphate to inorganic phosphate, which is important for the phosphate metabolism of cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 4-105369643-A-G is Benign according to our data. Variant chr4-105369643-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1212218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1497/149662) while in subpopulation AFR AF= 0.0344 (1395/40516). AF 95% confidence interval is 0.0329. There are 19 homozygotes in gnomad4. There are 665 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPA2	NM_176869.3	c.*82T>C		3_prime_UTR_variant	12/12	ENST00000341695.10
PPA2	NM_006903.4	c.*82T>C		3_prime_UTR_variant	11/11
PPA2	NM_176866.2	c.*82T>C		3_prime_UTR_variant	8/8
PPA2	NM_176867.3	c.*82T>C		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPA2	ENST00000341695.10	c.*82T>C		3_prime_UTR_variant	12/12	1	NM_176869.3	P1

Frequencies

GnomAD3 genomes AF: 0.00998 AC: 1492 AN: 149550 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000446

Gnomad OTH AF: 0.00829

GnomAD4 exome AF: 0.00118 AC: 1124 AN: 954158 Hom.: 21 Cov.: 16 AF XY: 0.000964 AC XY: 467 AN XY: 484346

Gnomad4 AFR exome AF: 0.0462

Gnomad4 AMR exome AF: 0.00309

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000486

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000386

Gnomad4 OTH exome AF: 0.00279

GnomAD4 genome AF: 0.0100 AC: 1497 AN: 149662 Hom.: 19 Cov.: 32 AF XY: 0.00911 AC XY: 665 AN XY: 73002

Gnomad4 AFR AF: 0.0344

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000446

Gnomad4 OTH AF: 0.00820

Alfa AF: 0.00458 Hom.: 0

Bravo AF: 0.0110

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	6.5
Dann	Benign	0.83

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: rs114230015; hg19: chr4-106290800;