Variant 12-62801959-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020700.2(PPM1H):c.613A>C(p.Thr205Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,612,446 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 20 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 11 hom. )

Consequence

PPM1H
NM_020700.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.62

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0088017285).

BP6

Variant 12-62801959-T-G is Benign according to our data. Variant chr12-62801959-T-G is described in ClinVar as [Benign]. Clinvar id is 788435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00854 (1298/152012) while in subpopulation AFR AF= 0.0303 (1256/41476). AF 95% confidence interval is 0.0289. There are 20 homozygotes in gnomad4. There are 614 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPM1H	NM_020700.2 link	c.613A>C	p.Thr205Pro	missense_variant	3/10	ENST00000228705.7	NP_065751.1	Q9ULR3
PPM1H	XM_011538578.3 link	c.499A>C	p.Thr167Pro	missense_variant	3/10		XP_011536880.1
PPM1H	XM_017019676.3 link	c.613A>C	p.Thr205Pro	missense_variant	3/9		XP_016875165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PPM1H	ENST00000228705.7 link	c.613A>C	p.Thr205Pro	missense_variant	3/10	1	NM_020700.2	ENSP00000228705.5	Q9ULR3
PPM1H	ENST00000547857.1 link	n.450A>C		non_coding_transcript_exon_variant	3/3	2
PPM1H	ENST00000548414.5 link	n.494A>C		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.00854

AC:

1297

AN:

151894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0303

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00671

GnomAD3 exomes

AF:

0.00210

AC:

516

AN:

245636

Hom.:

AF XY:

0.00170

AC XY:

228

AN XY:

133822

show subpopulations

Gnomad AFR exome

AF:

0.0323

Gnomad AMR exome

AF:

0.000639

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000543

Gnomad OTH exome

AF:

0.000668

GnomAD4 exome

AF:

0.000788

AC:

1151

AN:

1460434

Hom.:

Cov.:

AF XY:

0.000695

AC XY:

505

AN XY:

726398

show subpopulations

Gnomad4 AFR exome

AF:

0.0305

Gnomad4 AMR exome

AF:

0.000739

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00854

AC:

1298

AN:

152012

Hom.:

Cov.:

AF XY:

0.00826

AC XY:

614

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0303

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00419

Hom.:

Bravo

AF:

0.00945

ESP6500AA

AF:

0.0318

AC:

126

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.00266

AC:

322

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.49

DEOGEN2

Benign

0.034

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0088

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.24

REVEL

Benign

0.031

Sift

Benign

0.27

Sift4G

Benign

0.30

Polyphen

0.40

Vest4

0.46

MVP

0.082

MPC

0.60

ClinPred

0.0091

GERP RS

3.3

Varity_R

0.14

gMVP

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over