10-70233338-T-G

Variant names:

• chr10-70233338-T-G
• rs7077538
• NM_021129.4:c.-11A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021129.4(PPA1):​c.-11A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,534,116 control chromosomes in the GnomAD database, including 73,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5582 hom., cov: 33)
  • Exomes 𝑓: 0.31 (68212 hom.)
• Consequence: PPA1 NM_021129.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.334
• Publications: 21 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]

ENSG00000294344 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 10-70233338-T-G is Benign according to our data. Variant chr10-70233338-T-G is described in ClinVar as Benign. ClinVar VariationId is 403335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPA1	NM_021129.4	MANE Select	c.-11A>C		5_prime_UTR	Exon 1 of 11	NP_066952.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPA1	ENST00000373232.8	TSL:1 MANE Select	c.-11A>C		5_prime_UTR	Exon 1 of 11	ENSP00000362329.2
	PPA1	ENST00000625364.1	TSL:5	c.-11A>C		5_prime_UTR	Exon 1 of 7	ENSP00000486162.1
	PPA1	ENST00000495346.1	TSL:3	n.184+390A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37207 AN: 151916 Hom.: 5581 Cov.: 33

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.258

GnomAD2 exomes AF: 0.258 AC: 33528 AN: 129942 AF XY: 0.265

Gnomad AFR exome AF: 0.0895

Gnomad AMR exome AF: 0.171

Gnomad ASJ exome AF: 0.240

Gnomad EAS exome AF: 0.0357

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.307 AC: 423707 AN: 1382088 Hom.: 68212 Cov.: 35 AF XY: 0.306 AC XY: 208271 AN XY: 681672

African (AFR) AF: 0.0898 AC: 2679 AN: 29822

American (AMR) AF: 0.184 AC: 6376 AN: 34724

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 5889 AN: 24802

East Asian (EAS) AF: 0.0300 AC: 1036 AN: 34530

South Asian (SAS) AF: 0.285 AC: 22073 AN: 77546

European-Finnish (FIN) AF: 0.398 AC: 17257 AN: 43360

Middle Eastern (MID) AF: 0.258 AC: 1371 AN: 5310

European-Non Finnish (NFE) AF: 0.326 AC: 350808 AN: 1074518

Other (OTH) AF: 0.282 AC: 16218 AN: 57476

GnomAD4 genome AF: 0.245 AC: 37204 AN: 152028 Hom.: 5582 Cov.: 33 AF XY: 0.248 AC XY: 18456 AN XY: 74322

African (AFR) AF: 0.0998 AC: 4140 AN: 41474

American (AMR) AF: 0.210 AC: 3208 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 841 AN: 3464

East Asian (EAS) AF: 0.0364 AC: 188 AN: 5160

South Asian (SAS) AF: 0.284 AC: 1369 AN: 4828

European-Finnish (FIN) AF: 0.406 AC: 4298 AN: 10586

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.328 AC: 22287 AN: 67914

Other (OTH) AF: 0.255 AC: 538 AN: 2110

Alfa AF: 0.276 Hom.: 1236

Bravo AF: 0.220

Asia WGS AF: 0.153 AC: 534 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		0.33
PromoterAI		0.22	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs7077538; hg19: chr10-71993094;