12-62692811-A-G

Position:

• chr12-62692811-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.1137+1125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,050 control chromosomes in the GnomAD database, including 3,551 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 0.20 (3551 hom., cov: 32)
• Consequence: PPM1H NM_020700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.996

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPM1H	NM_020700.2	c.1137+1125T>C		intron_variant		ENST00000228705.7	NP_065751.1
PPM1H	XM_011538578.3	c.1023+1125T>C		intron_variant			XP_011536880.1
PPM1H	XM_017019676.3	c.1137+1125T>C		intron_variant			XP_016875165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1H	ENST00000228705.7	c.1137+1125T>C		intron_variant		1	NM_020700.2	ENSP00000228705	P1
PPM1H	ENST00000551214.5	n.539+1125T>C		intron_variant, non_coding_transcript_variant		3
PPM1H	ENST00000551519.1	n.527+1125T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29684 AN: 151932 Hom.: 3537 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.196 AC: 29746 AN: 152050 Hom.: 3551 Cov.: 32 AF XY: 0.198 AC XY: 14706 AN XY: 74332

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.188

Alfa AF: 0.149 Hom.: 2803

Bravo AF: 0.211

Asia WGS AF: 0.372 AC: 1290 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	0.85
DANN	Benign	0.59

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: rs342169; hg19: chr12-63086591;