rs12317552

Positions:

• chr12-62646830-C-T

Variant summary

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

The NM_020700.2(PPM1H):​c.*1659G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,184 control chromosomes in the GnomAD database, including 1,699 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 0.11 (1699 hom., cov: 32)
  • Exomes 𝑓: 0.056 (0 hom.)
• Consequence: PPM1H NM_020700.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489

Genes affected

PPM1H (HGNC:18583): (protein phosphatase, Mg2+/Mn2+ dependent 1H) Enables identical protein binding activity and phosphoprotein phosphatase activity. Predicted to be involved in protein dephosphorylation. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPM1H	NM_020700.2	c.*1659G>A		3_prime_UTR_variant	10/10	ENST00000228705.7
PPM1H	XM_011538578.3	c.*1659G>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1H	ENST00000228705.7	c.*1659G>A		3_prime_UTR_variant	10/10	1	NM_020700.2	P1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16934 AN: 152030 Hom.: 1693 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0201

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.0561

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0524

Gnomad OTH AF: 0.0880

GnomAD4 exome AF: 0.0556 AC: 2 AN: 36 Hom.: 0 Cov.: 0 AF XY: 0.0357 AC XY: 1 AN XY: 28

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.111 AC: 16950 AN: 152148 Hom.: 1699 Cov.: 32 AF XY: 0.107 AC XY: 7997 AN XY: 74392

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.0545

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.0391

Gnomad4 FIN AF: 0.0561

Gnomad4 NFE AF: 0.0524

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0625 Hom.: 439

Bravo AF: 0.120

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.49

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: rs12317552; hg19: chr12-63040610;