dbSNP rs2029721: PPM1H:c.870-17978C>T (chr12-62755564-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_020700.2(PPM1H):c.870-17978C>T variant causes a intron change. The variant allele was found at a frequency of 0.332 in 653,130 control chromosomes in the GnomAD database, including 38,593 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 0.29 ( 7471 hom., cov: 31)

Exomes 𝑓: 0.34 ( 31122 hom. )

Consequence

PPM1H
NM_020700.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.97

Publications

3 publications found

Variant links:

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]

PPM1H links:

GAPDHP44 (HGNC:37801): (glyceraldehyde 3 phosphate dehydrogenase pseudogene 44)

GAPDHP44 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=-0.52).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020700.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1H	NM_020700.2	MANE Select	c.870-17978C>T		intron	N/A	NP_065751.1	Q9ULR3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPM1H	ENST00000228705.7	TSL:1 MANE Select	c.870-17978C>T	intron	N/A	ENSP00000228705.5	Q9ULR3
PPM1H	ENST00000938249.1		c.900-17978C>T	intron	N/A	ENSP00000608308.1
GAPDHP44	ENST00000513513.1	TSL:6	n.338G>A	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43880

AN:

151888

Hom.:

7471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.435

Gnomad AMR

AF:

0.326

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.305

GnomAD4 exome

AF:

0.345

AC:

172767

AN:

501124

Hom.:

31122

Cov.:

AF XY:

0.341

AC XY:

92932

AN XY:

272180

show subpopulations

African (AFR)

AF:

0.112

AC:

1629

AN:

14600

American (AMR)

AF:

0.377

AC:

11627

AN:

30820

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

3881

AN:

14100

East Asian (EAS)

AF:

0.219

AC:

7101

AN:

32442

South Asian (SAS)

AF:

0.280

AC:

15675

AN:

56042

European-Finnish (FIN)

AF:

0.424

AC:

13528

AN:

31912

Middle Eastern (MID)

AF:

0.256

AC:

568

AN:

2216

European-Non Finnish (NFE)

AF:

0.376

AC:

109772

AN:

292164

Other (OTH)

AF:

0.335

AC:

8986

AN:

26828

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

5466

10932

16398

21864

27330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.289

AC:

43881

AN:

152006

Hom.:

7471

Cov.:

AF XY:

0.289

AC XY:

21506

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.113

AC:

4670

AN:

41504

American (AMR)

AF:

0.326

AC:

4983

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

997

AN:

3462

East Asian (EAS)

AF:

0.205

AC:

1058

AN:

5162

South Asian (SAS)

AF:

0.284

AC:

1369

AN:

4816

European-Finnish (FIN)

AF:

0.433

AC:

4566

AN:

10546

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.370

AC:

25129

AN:

67926

Other (OTH)

AF:

0.302

AC:

637

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1494

2987

4481

5974

7468

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.342

Hom.:

1242

Bravo

AF:

0.275

Asia WGS

AF:

0.240

AC:

839

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.1

(source)

DANN

Benign

0.78

PhyloP100

7.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over