chr19-46353850-C-T

Variant names:

• chr19-46353850-C-T
• NM_006247.4:c.224C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006247.4(PPP5C):​c.224C>T​(p.Thr75Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPP5C NM_006247.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.68
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006247.4. 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
	PPP5C	NM_006247.4	MANE Select	c.224C>T	p.Thr75Ile	missense	Exon 2 of 13	NP_006238.1	P53041
	PPP5C	NM_001204284.2		c.224C>T	p.Thr75Ile	missense	Exon 2 of 12	NP_001191213.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP5C	ENST00000012443.9	TSL:1 MANE Select	c.224C>T	p.Thr75Ile	missense	Exon 2 of 13	ENSP00000012443.4	P53041
	PPP5C	ENST00000478046.5	TSL:1	n.218C>T		non_coding_transcript_exon	Exon 2 of 14	ENSP00000434329.1	H0YDU8
	PPP5C	ENST00000391919.1	TSL:5	c.-95C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	ENSP00000375786.1	A8MU39

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.7
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.35
Sift	Benign	0.10	T
Sift4G	Benign	0.19	T
Polyphen		0.12	B
Vest4		0.69
MutPred		0.43		Loss of methylation at R74 (P = 0.2533)
MVP		0.81
MPC		0.80
ClinPred		0.85	D
GERP RS		5.0
Varity_R		0.25
gMVP		0.44
Mutation Taster		=32/68	disease causing

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

Other links and lift over

hg19: chr19-46857107;