chr19-46353988-C-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_006247.4(PPP5C):c.362C>T(p.Thr121Met) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000379 in 1,611,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000038 ( 0 hom. )
Consequence
PPP5C
NM_006247.4 missense, splice_region
NM_006247.4 missense, splice_region
Scores
2
4
13
Splicing: ADA: 0.9749
1
1
Clinical Significance
Conservation
PhyloP100: 5.46
Genes affected
PPP5C (HGNC:9322): (protein phosphatase 5 catalytic subunit) This gene encodes a serine/threonine phosphatase which is a member of the protein phosphatase catalytic subunit family. Proteins in this family participate in pathways regulated by reversible phosphorylation at serine and threonine residues; many of these pathways are involved in the regulation of cell growth and differentiation. The product of this gene has been shown to participate in signaling pathways in response to hormones or cellular stress, and elevated levels of this protein may be associated with breast cancer development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.1875669).
BS2
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPP5C | NM_006247.4 | c.362C>T | p.Thr121Met | missense_variant, splice_region_variant | 2/13 | ENST00000012443.9 | |
PPP5C | NM_001204284.2 | c.362C>T | p.Thr121Met | missense_variant, splice_region_variant | 2/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP5C | ENST00000012443.9 | c.362C>T | p.Thr121Met | missense_variant, splice_region_variant | 2/13 | 1 | NM_006247.4 | P1 | |
PPP5C | ENST00000478046.5 | c.359C>T | p.Thr120Met | missense_variant, splice_region_variant, NMD_transcript_variant | 2/14 | 1 | |||
PPP5C | ENST00000391919.1 | c.44C>T | p.Thr15Met | missense_variant, splice_region_variant | 2/12 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152212Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
6
AN:
152212
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000124 AC: 3AN: 241978Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131468
GnomAD3 exomes
AF:
AC:
3
AN:
241978
Hom.:
AF XY:
AC XY:
2
AN XY:
131468
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000377 AC: 55AN: 1458812Hom.: 0 Cov.: 32 AF XY: 0.0000276 AC XY: 20AN XY: 725572
GnomAD4 exome
AF:
AC:
55
AN:
1458812
Hom.:
Cov.:
32
AF XY:
AC XY:
20
AN XY:
725572
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74360
GnomAD4 genome
AF:
AC:
6
AN:
152212
Hom.:
Cov.:
33
AF XY:
AC XY:
3
AN XY:
74360
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 31, 2024 | The c.362C>T (p.T121M) alteration is located in exon 2 (coding exon 2) of the PPP5C gene. This alteration results from a C to T substitution at nucleotide position 362, causing the threonine (T) at amino acid position 121 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MutPred
Loss of phosphorylation at T121 (P = 0.0424);.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at