NM_020700.2:c.1398-2839T>C

Variant names:

• chr12-62651475-A-G
• rs10506445
• NM_020700.2:c.1398-2839T>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.1398-2839T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 152,322 control chromosomes in the GnomAD database, including 155 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 0.038 (155 hom., cov: 32)
• Consequence: PPM1H NM_020700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429
• Publications: 3 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]

LOC124903103 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1H	NM_020700.2	c.1398-2839T>C		intron_variant	Intron 9 of 9	ENST00000228705.7	NP_065751.1
PPM1H	XM_011538578.3	c.1284-2839T>C		intron_variant	Intron 9 of 9		XP_011536880.1
LOC124903103	XR_007063640.1	n.*197A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1H	ENST00000228705.7	c.1398-2839T>C		intron_variant	Intron 9 of 9	1	NM_020700.2	ENSP00000228705.5
PPM1H	ENST00000551214.5	n.800-2839T>C		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 5775 AN: 152204 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.00943

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0426

Gnomad FIN AF: 0.0572

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0397

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

GnomAD4 genome AF: 0.0379 AC: 5769 AN: 152322 Hom.: 155 Cov.: 32 AF XY: 0.0372 AC XY: 2774 AN XY: 74492

African (AFR) AF: 0.00940 AC: 391 AN: 41586

American (AMR) AF: 0.0258 AC: 394 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.0425 AC: 205 AN: 4828

European-Finnish (FIN) AF: 0.0572 AC: 607 AN: 10618

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0542 AC: 3686 AN: 68024

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

Alfa AF: 0.0479 Hom.: 223

Bravo AF: 0.0344

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.75
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism

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: rs10506445; hg19: chr12-63045255;