chr9-125189693-T-C

Position:

• chr9-125189693-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002721.5(PPP6C):​c.26A>G​(p.Tyr9Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000754 in 1,458,200 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: PPP6C NM_002721.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.68

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP6C	NM_002721.5	c.26A>G	p.Tyr9Cys	missense_variant	1/7	ENST00000373547.9	NP_002712.1
PPP6C	NM_001123355.2	c.26A>G	p.Tyr9Cys	missense_variant	1/8		NP_001116827.1
PPP6C	NM_001123369.2	c.26A>G	p.Tyr9Cys	missense_variant	1/6		NP_001116841.1
PPP6C	XM_047423566.1	c.26A>G	p.Tyr9Cys	missense_variant	1/7		XP_047279522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP6C	ENST00000373547.9	c.26A>G	p.Tyr9Cys	missense_variant	1/7	1	NM_002721.5	ENSP00000362648.4
PPP6C	ENST00000451402.5	c.26A>G	p.Tyr9Cys	missense_variant	1/8	2		ENSP00000392147.1
PPP6C	ENST00000415905.5	c.26A>G	p.Tyr9Cys	missense_variant	1/6	2		ENSP00000411744.1
PPP6C	ENST00000456642.1	c.-104A>G		5_prime_UTR_variant	1/6	3		ENSP00000416287.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1458200 Hom.: 0 Cov.: 34 AF XY: 0.00000827 AC XY: 6 AN XY: 725506

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000990

Gnomad4 OTH exome AF: 0.00

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

Feb 10, 2022

The c.26A>G (p.Y9C) alteration is located in exon 1 (coding exon 1) of the PPP6C gene. This alteration results from a A to G substitution at nucleotide position 26, causing the tyrosine (Y) at amino acid position 9 to be replaced by a cysteine (C). 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
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.0090	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	T;.;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.031
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	T;D;T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Uncertain	0.30
Sift	Benign	0.059	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.85
MutPred		0.46		Gain of methylation at K8 (P = 0.0157);Gain of methylation at K8 (P = 0.0157);Gain of methylation at K8 (P = 0.0157);
MVP		0.65
MPC		2.0
ClinPred		0.91	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.74

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: chr9-127951972;