12-62887666-G-C

Variant names:

• chr12-62887666-G-C
• rs10784318
• NM_020700.2:c.245+46826C>G

Variant summary

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

The NM_020700.2(PPM1H):​c.245+46826C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,048 control chromosomes in the GnomAD database, including 8,722 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 0.33 (8722 hom., cov: 32)
• Consequence: PPM1H NM_020700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450
• Publications: 4 publications found

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]

LOC105369795 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020700.2. 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
	PPM1H	NM_020700.2	MANE Select	c.245+46826C>G		intron	N/A	NP_065751.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1H	ENST00000228705.7	TSL:1 MANE Select	c.245+46826C>G		intron	N/A	ENSP00000228705.5
	PPM1H	ENST00000548414.5	TSL:3	n.126+46257C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50077 AN: 151930 Hom.: 8695 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.330 AC: 50138 AN: 152048 Hom.: 8722 Cov.: 32 AF XY: 0.336 AC XY: 24986 AN XY: 74330

African (AFR) AF: 0.291 AC: 12068 AN: 41478

American (AMR) AF: 0.433 AC: 6613 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3466

East Asian (EAS) AF: 0.555 AC: 2868 AN: 5164

South Asian (SAS) AF: 0.477 AC: 2295 AN: 4812

European-Finnish (FIN) AF: 0.262 AC: 2764 AN: 10558

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21188 AN: 67980

Other (OTH) AF: 0.348 AC: 735 AN: 2110

Alfa AF: 0.155 Hom.: 252

Bravo AF: 0.344

Asia WGS AF: 0.510 AC: 1772 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.82
PhyloP100		0.45
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: rs10784318; hg19: chr12-63281446;