NM_177983.3:c.410-160G>A

Variant names:

• chr2-27385248-C-T
• rs1647284
• NM_177983.3:c.410-160G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177983.3(PPM1G):​c.410-160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 724,412 control chromosomes in the GnomAD database, including 63,091 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 0.47 (18597 hom., cov: 32)
  • Exomes 𝑓: 0.38 (44494 hom.)
• Consequence: PPM1G NM_177983.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177983.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1G	NM_177983.3	MANE Select	c.410-160G>A		intron	N/A	NP_817092.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1G	ENST00000344034.5	TSL:1 MANE Select	c.410-160G>A		intron	N/A	ENSP00000342778.4
	PPM1G	ENST00000472077.1	TSL:2	n.2164G>A		non_coding_transcript_exon	Exon 2 of 8

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71493 AN: 151890 Hom.: 18549 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.380 AC: 217550 AN: 572404 Hom.: 44494 Cov.: 8 AF XY: 0.381 AC XY: 110986 AN XY: 291552

African (AFR) AF: 0.694 AC: 9764 AN: 14070

American (AMR) AF: 0.513 AC: 6720 AN: 13100

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 4612 AN: 13830

East Asian (EAS) AF: 0.125 AC: 3642 AN: 29170

South Asian (SAS) AF: 0.408 AC: 15668 AN: 38440

European-Finnish (FIN) AF: 0.429 AC: 12353 AN: 28826

Middle Eastern (MID) AF: 0.327 AC: 715 AN: 2184

European-Non Finnish (NFE) AF: 0.378 AC: 152541 AN: 403168

Other (OTH) AF: 0.389 AC: 11535 AN: 29616

GnomAD4 genome AF: 0.471 AC: 71607 AN: 152008 Hom.: 18597 Cov.: 32 AF XY: 0.469 AC XY: 34842 AN XY: 74268

African (AFR) AF: 0.691 AC: 28626 AN: 41438

American (AMR) AF: 0.474 AC: 7235 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1157 AN: 3468

East Asian (EAS) AF: 0.154 AC: 798 AN: 5178

South Asian (SAS) AF: 0.426 AC: 2055 AN: 4820

European-Finnish (FIN) AF: 0.428 AC: 4518 AN: 10564

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26035 AN: 67970

Other (OTH) AF: 0.415 AC: 872 AN: 2102

Alfa AF: 0.448 Hom.: 2694

Bravo AF: 0.483

Asia WGS AF: 0.363 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.81
DANN	Benign	0.49
PhyloP100		-0.85
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: rs1647284; hg19: chr2-27608115;