rs1249935

Variant names:

• chr12-62924520-C-A
• rs1249935
• NM_020700.2:c.245+9972G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-62924520-C-A
• chr12-62924520-C-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.245+9972G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,244 control chromosomes in the GnomAD database, including 61,643 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 0.90 (61643 hom., cov: 33)
• Consequence: PPM1H NM_020700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1H	NM_020700.2	c.245+9972G>T		intron_variant	Intron 1 of 9	ENST00000228705.7	NP_065751.1
PPM1H	XM_011538578.3	c.131+9403G>T		intron_variant	Intron 1 of 9		XP_011536880.1
PPM1H	XM_017019676.3	c.245+9972G>T		intron_variant	Intron 1 of 8		XP_016875165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1H	ENST00000228705.7	c.245+9972G>T		intron_variant	Intron 1 of 9	1	NM_020700.2	ENSP00000228705.5
PPM1H	ENST00000548414.5	n.126+9403G>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136534 AN: 152126 Hom.: 61617 Cov.: 33

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.914

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

GnomAD4 genome AF: 0.897 AC: 136609 AN: 152244 Hom.: 61643 Cov.: 33 AF XY: 0.896 AC XY: 66693 AN XY: 74436

African (AFR) AF: 0.790 AC: 32804 AN: 41516

American (AMR) AF: 0.932 AC: 14262 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 3273 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5165 AN: 5182

South Asian (SAS) AF: 0.961 AC: 4640 AN: 4828

European-Finnish (FIN) AF: 0.901 AC: 9543 AN: 10590

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.938 AC: 63825 AN: 68034

Other (OTH) AF: 0.915 AC: 1936 AN: 2116

Alfa AF: 0.925 Hom.: 104198

Bravo AF: 0.896

Asia WGS AF: 0.963 AC: 3351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.32
DANN	Benign	0.53
PhyloP100		-1.7
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: rs1249935; hg19: chr12-63318300;