9-125189931-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000451402.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP6C	NM_002721.5	MANE Select	c.-213C>A		upstream_gene	N/A	NP_002712.1
	PPP6C	NM_001123355.2		c.-213C>A		upstream_gene	N/A	NP_001116827.1
	PPP6C	NM_001123369.2		c.-213C>A		upstream_gene	N/A	NP_001116841.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP6C	ENST00000451402.5	TSL:2	c.-213C>A		5_prime_UTR	Exon 1 of 8	ENSP00000392147.1
	PPP6C	ENST00000415905.5	TSL:2	c.-213C>A		5_prime_UTR	Exon 1 of 6	ENSP00000411744.1
	PPP6C	ENST00000373547.9	TSL:1 MANE Select	c.-213C>A		upstream_gene	N/A	ENSP00000362648.4

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

African (AFR) AF: 0.480 AC: 3891 AN: 8098

American (AMR) AF: 0.314 AC: 3802 AN: 12092

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 6077 AN: 11952

East Asian (EAS) AF: 0.549 AC: 13149 AN: 23968

South Asian (SAS) AF: 0.395 AC: 15913 AN: 40250

European-Finnish (FIN) AF: 0.308 AC: 8450 AN: 27452

Middle Eastern (MID) AF: 0.455 AC: 823 AN: 1810

European-Non Finnish (NFE) AF: 0.451 AC: 117833 AN: 261292

Other (OTH) AF: 0.447 AC: 10527 AN: 23534

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

African (AFR) AF: 0.476 AC: 19743 AN: 41446

American (AMR) AF: 0.370 AC: 5653 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1762 AN: 3470

East Asian (EAS) AF: 0.537 AC: 2763 AN: 5148

South Asian (SAS) AF: 0.411 AC: 1983 AN: 4828

European-Finnish (FIN) AF: 0.292 AC: 3090 AN: 10570

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30820 AN: 67946

Other (OTH) AF: 0.447 AC: 944 AN: 2114

Alfa AF: 0.440 Hom.: 8291

Bravo AF: 0.452

Asia WGS AF: 0.498 AC: 1729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.38
DANN	Benign	0.78
PhyloP100		-1.9
PromoterAI		-0.052	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs459311; hg19: chr9-127952210;