9-125189597-G-C

Position:

• chr9-125189597-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001123355.2(PPP6C):​c.122C>G​(p.Ala41Gly) 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. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPP6C NM_001123355.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05

Genes affected

PPP6C (HGNC:9323): (protein phosphatase 6 catalytic subunit) This gene encodes the catalytic subunit of protein phosphatase, a component of a signaling pathway regulating cell cycle progression. Splice variants encoding different protein isoforms exist. The pseudogene of this gene is located on chromosome X. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10225561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP6C	NM_002721.5	c.75+47C>G		intron_variant		ENST00000373547.9	NP_002712.1
PPP6C	NM_001123355.2	c.122C>G	p.Ala41Gly	missense_variant	1/8		NP_001116827.1
PPP6C	XM_047423566.1	c.122C>G	p.Ala41Gly	missense_variant	1/7		XP_047279522.1
PPP6C	NM_001123369.2	c.75+47C>G		intron_variant			NP_001116841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP6C	ENST00000373547.9	c.75+47C>G		intron_variant		1	NM_002721.5	ENSP00000362648.4
PPP6C	ENST00000451402.5	c.122C>G	p.Ala41Gly	missense_variant	1/8	2		ENSP00000392147.1
PPP6C	ENST00000415905.5	c.75+47C>G		intron_variant		2		ENSP00000411744.1
PPP6C	ENST00000456642.1	c.-55+47C>G		intron_variant		3		ENSP00000416287.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.122C>G (p.A41G) alteration is located in exon 1 (coding exon 1) of the PPP6C gene. This alteration results from a C to G substitution at nucleotide position 122, causing the alanine (A) at amino acid position 41 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Uncertain	0.99
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.97	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.033
Sift	Benign	0.20	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.34		Gain of relative solvent accessibility (P = 0.0166);
MVP		0.17
MPC		1.5
ClinPred		0.61	D
GERP RS		2.2
gMVP		0.15

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: chr9-127951876;