rs572873

Variant names:

• chr12-62872037-A-C
• rs572873
• NM_020700.2:c.246-39758T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-62872037-A-C
• chr12-62872037-A-G
• chr12-62872037-A-T

Variant summary

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

The NM_020700.2(PPM1H):​c.246-39758T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,020 control chromosomes in the GnomAD database, including 32,674 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 0.64 (32674 hom., cov: 32)
• Consequence: PPM1H NM_020700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• 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]

LOC105369795 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1H	NM_020700.2	c.246-39758T>G		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.246-39758T>G		intron_variant	Intron 1 of 9	1	NM_020700.2	ENSP00000228705.5
PPM1H	ENST00000548414.5	n.127-39758T>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97932 AN: 151902 Hom.: 32623 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.645 AC: 98036 AN: 152020 Hom.: 32674 Cov.: 32 AF XY: 0.642 AC XY: 47728 AN XY: 74312

African (AFR) AF: 0.814 AC: 33778 AN: 41474

American (AMR) AF: 0.696 AC: 10633 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2178 AN: 3470

East Asian (EAS) AF: 0.590 AC: 3048 AN: 5166

South Asian (SAS) AF: 0.645 AC: 3110 AN: 4818

European-Finnish (FIN) AF: 0.464 AC: 4893 AN: 10556

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38343 AN: 67946

Other (OTH) AF: 0.652 AC: 1376 AN: 2110

Alfa AF: 0.538 Hom.: 2676

Bravo AF: 0.671

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.5
DANN	Benign	0.81
PhyloP100		0.11
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: rs572873; hg19: chr12-63265817; COSMIC: COSV107209942;