12-62651475-A-G

Position:

• chr12-62651475-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000228705.7(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 ENST00000228705.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PPM1H	NM_020700.2	c.1398-2839T>C		intron_variant		ENST00000228705.7	NP_065751.1
PPM1H	XM_011538578.3	c.1284-2839T>C		intron_variant			XP_011536880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1H	ENST00000228705.7	c.1398-2839T>C		intron_variant		1	NM_020700.2	ENSP00000228705	P1
PPM1H	ENST00000551214.5	n.800-2839T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.00940

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0425

Gnomad4 FIN AF: 0.0572

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0472 Hom.: 183

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

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: rs10506445; hg19: chr12-63045255;