rs1249935

chr12-62924520-C-Achr12-62924520-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.245+9972G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,244 control chromosomes in the GnomAD database, including 61,643 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 0.90 (61643 hom., cov: 33)
• Consequence: PPM1H NM_020700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPM1H	NM_020700.2	c.245+9972G>T		intron_variant		ENST00000228705.7
PPM1H	XM_011538578.3	c.131+9403G>T		intron_variant
PPM1H	XM_017019676.3	c.245+9972G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1H	ENST00000228705.7	c.245+9972G>T		intron_variant		1	NM_020700.2	P1
PPM1H	ENST00000548414.5	n.126+9403G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136534 AN: 152126 Hom.: 61617 Cov.: 33

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.914

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

GnomAD4 genome AF: 0.897 AC: 136609 AN: 152244 Hom.: 61643 Cov.: 33 AF XY: 0.896 AC XY: 66693 AN XY: 74436

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.932

Gnomad4 ASJ AF: 0.943

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.961

Gnomad4 FIN AF: 0.901

Gnomad4 NFE AF: 0.938

Gnomad4 OTH AF: 0.915

Alfa AF: 0.929 Hom.: 71793

Bravo AF: 0.896

Asia WGS AF: 0.963 AC: 3351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.32
Dann	Benign	0.53

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: rs1249935; hg19: chr12-63318300;