Genetic Variant NM_020700.2:c.*1659G>A (chr12-62646830-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_020700.2(PPM1H):c.*1659G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,184 control chromosomes in the GnomAD database, including 1,699 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 0.11 ( 1699 hom., cov: 32)

Exomes 𝑓: 0.056 ( 0 hom. )

Consequence

PPM1H
NM_020700.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.489

Publications

4 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:

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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1H	NM_020700.2 link	c.*1659G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000228705.7	NP_065751.1	Q9ULR3
PPM1H	XM_011538578.3 link	c.*1659G>A		3_prime_UTR_variant	Exon 10 of 10		XP_011536880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1H	ENST00000228705.7 link	c.*1659G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_020700.2	ENSP00000228705.5		Q9ULR3

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16934

AN:

152030

Hom.:

1693

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0546

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.0201

Gnomad SAS

AF:

0.0395

Gnomad FIN

AF:

0.0561

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0524

Gnomad OTH

AF:

0.0880

GnomAD4 exome

AF:

0.0556

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0357

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.111

AC:

16950

AN:

152148

Hom.:

1699

Cov.:

AF XY:

0.107

AC XY:

7997

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.267

AC:

11081

AN:

41472

American (AMR)

AF:

0.0545

AC:

833

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

348

AN:

3466

East Asian (EAS)

AF:

0.0199

AC:

103

AN:

5172

South Asian (SAS)

AF:

0.0391

AC:

189

AN:

4834

European-Finnish (FIN)

AF:

0.0561

AC:

594

AN:

10594

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0524

AC:

3562

AN:

68000

Other (OTH)

AF:

0.0866

AC:

183

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

684

1369

2053

2738

3422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0711

Hom.:

788

Bravo

AF:

0.120

Asia WGS

AF:

0.0460

AC:

159

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.7

(source)

DANN

Benign

0.49

PhyloP100

0.49

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over