rs342169

Variant names:

• chr12-62692811-A-G
• rs342169
• NM_020700.2:c.1137+1125T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-62692811-A-G
• chr12-62692811-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.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
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPM1H	NM_020700.2	c.1137+1125T>C		intron_variant	Intron 7 of 9	ENST00000228705.7	NP_065751.1
PPM1H	XM_011538578.3	c.1023+1125T>C		intron_variant	Intron 7 of 9		XP_011536880.1
PPM1H	XM_017019676.3	c.1137+1125T>C		intron_variant	Intron 7 of 8		XP_016875165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1H	ENST00000228705.7	c.1137+1125T>C		intron_variant	Intron 7 of 9	1	NM_020700.2	ENSP00000228705.5
PPM1H	ENST00000551214.5	n.539+1125T>C		intron_variant	Intron 3 of 5	3
PPM1H	ENST00000551519.1	n.527+1125T>C		intron_variant	Intron 4 of 4	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

African (AFR) AF: 0.241 AC: 9993 AN: 41466

American (AMR) AF: 0.274 AC: 4185 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3470

East Asian (EAS) AF: 0.530 AC: 2733 AN: 5152

South Asian (SAS) AF: 0.230 AC: 1105 AN: 4798

European-Finnish (FIN) AF: 0.120 AC: 1271 AN: 10586

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9132 AN: 67982

Other (OTH) AF: 0.188 AC: 398 AN: 2114

Alfa AF: 0.157 Hom.: 4291

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
PhyloP100		-1.0
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: rs342169; hg19: chr12-63086591;