rs163688

Positions:

• chr12-62698352-C-T

Variant summary

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

The NM_020700.2(PPM1H):​c.1074-4353G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,002 control chromosomes in the GnomAD database, including 9,228 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 0.32 (9228 hom., cov: 32)
• Consequence: PPM1H NM_020700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.34

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPM1H	NM_020700.2	c.1074-4353G>A		intron_variant		ENST00000228705.7	NP_065751.1
PPM1H	XM_011538578.3	c.960-4353G>A		intron_variant			XP_011536880.1
PPM1H	XM_017019676.3	c.1074-4353G>A		intron_variant			XP_016875165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1H	ENST00000228705.7	c.1074-4353G>A		intron_variant		1	NM_020700.2	ENSP00000228705	P1
PPM1H	ENST00000551214.5	n.476-4353G>A		intron_variant, non_coding_transcript_variant		3
PPM1H	ENST00000551519.1	n.464-4353G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49289 AN: 151884 Hom.: 9192 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.325 AC: 49393 AN: 152002 Hom.: 9228 Cov.: 32 AF XY: 0.327 AC XY: 24310 AN XY: 74296

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.272

Alfa AF: 0.236 Hom.: 6001

Bravo AF: 0.340

Asia WGS AF: 0.397 AC: 1377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.013
DANN	Benign	0.63

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: rs163688; hg19: chr12-63092132;