9-125148219-G-T

Variant names:

• chr9-125148219-G-T
• rs1048251
• NM_002721.5:c.*1454C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002721.5(PPP6C):​c.*1454C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 154,398 control chromosomes in the GnomAD database, including 15,435 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 (15256 hom., cov: 32)
  • Exomes 𝑓: 0.37 (179 hom.)
• Consequence: PPP6C NM_002721.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 10 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=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002721.5. 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.*1454C>A		3_prime_UTR	Exon 7 of 7	NP_002712.1
	PPP6C	NM_001123355.2		c.*1454C>A		3_prime_UTR	Exon 8 of 8	NP_001116827.1
	PPP6C	NM_001123369.2		c.*1454C>A		3_prime_UTR	Exon 6 of 6	NP_001116841.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP6C	ENST00000373547.9	TSL:1 MANE Select	c.*1454C>A		3_prime_UTR	Exon 7 of 7	ENSP00000362648.4
	PPP6C	ENST00000451402.5	TSL:2	c.*1454C>A		3_prime_UTR	Exon 8 of 8	ENSP00000392147.1
	PPP6C	ENST00000415905.5	TSL:2	c.*1454C>A		3_prime_UTR	Exon 6 of 6	ENSP00000411744.1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67208 AN: 151846 Hom.: 15235 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.442

GnomAD4 exome AF: 0.374 AC: 911 AN: 2434 Hom.: 179 Cov.: 0 AF XY: 0.380 AC XY: 624 AN XY: 1644

African (AFR) AF: 0.545 AC: 12 AN: 22

American (AMR) AF: 0.165 AC: 35 AN: 212

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 36 AN: 78

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.352 AC: 191 AN: 542

European-Finnish (FIN) AF: 0.222 AC: 8 AN: 36

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.409 AC: 606 AN: 1482

Other (OTH) AF: 0.367 AC: 22 AN: 60

GnomAD4 genome AF: 0.443 AC: 67269 AN: 151964 Hom.: 15256 Cov.: 32 AF XY: 0.434 AC XY: 32203 AN XY: 74272

African (AFR) AF: 0.476 AC: 19737 AN: 41448

American (AMR) AF: 0.370 AC: 5646 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1749 AN: 3468

East Asian (EAS) AF: 0.530 AC: 2745 AN: 5182

South Asian (SAS) AF: 0.410 AC: 1976 AN: 4818

European-Finnish (FIN) AF: 0.294 AC: 3099 AN: 10538

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.454 AC: 30819 AN: 67928

Other (OTH) AF: 0.448 AC: 946 AN: 2110

Alfa AF: 0.452 Hom.: 18732

Bravo AF: 0.451

Asia WGS AF: 0.495 AC: 1717 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.8
DANN	Benign	0.71
PhyloP100		0.086
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs1048251; hg19: chr9-127910498;