dbSNP rs1647284: PPM1G:c.410-160G>A (chr2-27385248-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.848

Publications

13 publications found

Variant links:

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]

PPM1G links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1G	NM_177983.3 link	c.410-160G>A		intron_variant	Intron 4 of 9	ENST00000344034.5	NP_817092.1	O15355Q6IAU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1G	ENST00000344034.5 link	c.410-160G>A		intron_variant	Intron 4 of 9	1	NM_177983.3	ENSP00000342778.4		O15355
PPM1G	ENST00000472077.1 link	n.2164G>A		non_coding_transcript_exon_variant	Exon 2 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71493

AN:

151890

Hom.:

18549

Cov.:

show subpopulations

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.:

AF XY:

0.381

AC XY:

110986

AN XY:

291552

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

6425

12850

19276

25701

32126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3032

6064

9096

12128

15160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.471

AC:

71607

AN:

152008

Hom.:

18597

Cov.:

AF XY:

0.469

AC XY:

34842

AN XY:

74268

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1780

3559

5339

7118

8898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.81

(source)

DANN

Benign

0.49

PhyloP100

-0.85

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over