NM_020700.2:c.246-8206T>C

Variant names:

• chr12-62840485-A-G
• rs10506451
• NM_020700.2:c.246-8206T>C

Variant summary

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

The NM_020700.2(PPM1H):​c.246-8206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,032 control chromosomes in the GnomAD database, including 26,797 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 0.55 (26797 hom., cov: 31)
• Consequence: PPM1H NM_020700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1H	NM_020700.2	c.246-8206T>C		intron_variant	Intron 1 of 9	ENST00000228705.7	NP_065751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1H	ENST00000228705.7	c.246-8206T>C		intron_variant	Intron 1 of 9	1	NM_020700.2	ENSP00000228705.5
PPM1H	ENST00000548414.5	n.127-8206T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84360 AN: 151914 Hom.: 26802 Cov.: 31

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.555 AC: 84371 AN: 152032 Hom.: 26797 Cov.: 31 AF XY: 0.561 AC XY: 41673 AN XY: 74296

African (AFR) AF: 0.230 AC: 9534 AN: 41482

American (AMR) AF: 0.585 AC: 8929 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2388 AN: 3470

East Asian (EAS) AF: 0.605 AC: 3113 AN: 5148

South Asian (SAS) AF: 0.547 AC: 2635 AN: 4816

European-Finnish (FIN) AF: 0.797 AC: 8413 AN: 10550

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47461 AN: 67976

Other (OTH) AF: 0.575 AC: 1214 AN: 2112

Alfa AF: 0.645 Hom.: 62760

Bravo AF: 0.526

Asia WGS AF: 0.542 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.50
PhyloP100		-0.42
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: rs10506451; hg19: chr12-63234265;