12-62840485-A-G

Position:

• chr12-62840485-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PPM1H	NM_020700.2	c.246-8206T>C		intron_variant		ENST00000228705.7	NP_065751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1H	ENST00000228705.7	c.246-8206T>C		intron_variant		1	NM_020700.2	ENSP00000228705.5
PPM1H	ENST00000548414.5	n.127-8206T>C		intron_variant		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

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.797

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.575

Alfa AF: 0.661 Hom.: 47283

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

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: rs10506451; hg19: chr12-63234265;