17-60600551-C-T

Variant names:

• chr17-60600551-C-T
• NM_003620.4:c.137C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_003620.4(PPM1D):​c.137C>T​(p.Ser46Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPM1D NM_003620.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.07

Genes affected

PPM1D (HGNC:9277): (protein phosphatase, Mg2+/Mn2+ dependent 1D) 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. The expression of this gene is induced in a p53-dependent manner in response to various environmental stresses. While being induced by tumor suppressor protein TP53/p53, this phosphatase negatively regulates the activity of p38 MAP kinase, MAPK/p38, through which it reduces the phosphorylation of p53, and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis. This gene is located in a chromosomal region known to be amplified in breast cancer. The amplification of this gene has been detected in both breast cancer cell line and primary breast tumors, which suggests a role of this gene in cancer development. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13656753).
• BP6: Variant 17-60600551-C-T is Benign according to our data. Variant chr17-60600551-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3675787.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1D	NM_003620.4	c.137C>T	p.Ser46Phe	missense_variant	Exon 1 of 6	ENST00000305921.8	NP_003611.1
PPM1D	XR_007065507.1	n.359C>T		non_coding_transcript_exon_variant	Exon 1 of 7
PPM1D	XR_934577.3	n.359C>T		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1D	ENST00000305921.8	c.137C>T	p.Ser46Phe	missense_variant	Exon 1 of 6	1	NM_003620.4	ENSP00000306682.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.34	.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.75	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.2	.;N
REVEL	Benign	0.047
Sift	Uncertain	0.024	.;D
Sift4G	Benign	0.12	T;T
Polyphen		0.29	.;B
Vest4		0.17
MutPred		0.26		Loss of phosphorylation at S46 (P = 0.0017);Loss of phosphorylation at S46 (P = 0.0017);
MVP		0.57
MPC		1.3
ClinPred		0.47	T
GERP RS		4.7
Varity_R		0.20
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-58677912;