12-62887666-G-C

Position:

• chr12-62887666-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPM1H	NM_020700.2	c.245+46826C>G		intron_variant		ENST00000228705.7
LOC105369795	XR_945016.3	n.400-8442G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1H	ENST00000228705.7	c.245+46826C>G		intron_variant		1	NM_020700.2	P1
PPM1H	ENST00000548414.5	n.126+46257C>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.348

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.82

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: rs10784318; hg19: chr12-63281446;