rs12476704

Positions:

• chr2-27390164-C-A

Variant summary

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

The NM_177983.3(PPM1G):​c.121-3006G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,722 control chromosomes in the GnomAD database, including 11,041 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 0.38 (11041 hom., cov: 31)
• Consequence: PPM1G NM_177983.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

Genes affected

PPM1G (HGNC:9278): (protein phosphatase, Mg2+/Mn2+ dependent 1G) The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase is found to be responsible for the dephosphorylation of Pre-mRNA splicing factors, which is important for the formation of functional spliceosome. Studies of a similar gene in mice suggested a role of this phosphatase in regulating cell cycle progression. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPM1G	NM_177983.3	c.121-3006G>T		intron_variant		ENST00000344034.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1G	ENST00000344034.5	c.121-3006G>T		intron_variant		1	NM_177983.3	P1
PPM1G	ENST00000472077.1	n.254-3006G>T		intron_variant, non_coding_transcript_variant		2
PPM1G	ENST00000484925.1	n.274-3006G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56878 AN: 151604 Hom.: 11019 Cov.: 31

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.375 AC: 56930 AN: 151722 Hom.: 11041 Cov.: 31 AF XY: 0.376 AC XY: 27837 AN XY: 74126

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.353

Alfa AF: 0.379 Hom.: 1383

Bravo AF: 0.375

Asia WGS AF: 0.338 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.49

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: rs12476704; hg19: chr2-27613031;