9-125189931-G-T

Variant names:

• chr9-125189931-G-T
• rs459311
• ENST00000451402.5:c.-213C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000451402.5(PPP6C):​c.-213C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 562,458 control chromosomes in the GnomAD database, including 56,169 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (15275 hom., cov: 32)
  • Exomes 𝑓: 0.44 (40894 hom.)
• Consequence: PPP6C ENST00000451402.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP6C	NM_002721.5	c.-213C>A		upstream_gene_variant		ENST00000373547.9	NP_002712.1
PPP6C	NM_001123355.2	c.-213C>A		upstream_gene_variant			NP_001116827.1
PPP6C	NM_001123369.2	c.-213C>A		upstream_gene_variant			NP_001116841.1
PPP6C	XM_047423566.1	c.-213C>A		upstream_gene_variant			XP_047279522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP6C	ENST00000451402.5	c.-213C>A		5_prime_UTR_variant	Exon 1 of 8	2		ENSP00000392147.1
PPP6C	ENST00000415905.5	c.-213C>A		5_prime_UTR_variant	Exon 1 of 6	2		ENSP00000411744.1
PPP6C	ENST00000373547.9	c.-213C>A		upstream_gene_variant		1	NM_002721.5	ENSP00000362648.4
PPP6C	ENST00000456642.1	c.-342C>A		upstream_gene_variant		3		ENSP00000416287.1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67248 AN: 151892 Hom.: 15254 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.440

GnomAD4 exome AF: 0.440 AC: 180465 AN: 410448 Hom.: 40894 Cov.: 5 AF XY: 0.438 AC XY: 94526 AN XY: 215656

Gnomad4 AFR exome AF: 0.480

Gnomad4 AMR exome AF: 0.314

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.549

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.451

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.443 AC: 67310 AN: 152010 Hom.: 15275 Cov.: 32 AF XY: 0.434 AC XY: 32222 AN XY: 74304

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.447

Alfa AF: 0.441 Hom.: 4689

Bravo AF: 0.452

Asia WGS AF: 0.498 AC: 1729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.38
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs459311; hg19: chr9-127952210;