NM_002721.5:c.*2883G>A

Variant names:

• chr9-125146790-C-T
• rs6744
• NM_002721.5:c.*2883G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002721.5(PPP6C):​c.*2883G>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 0.443 in 151,904 control chromosomes in the GnomAD database, including 15,240 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 (15240 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PPP6C NM_002721.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• 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.*2883G>A		3_prime_UTR	Exon 7 of 7	NP_002712.1
	PPP6C	NM_001123355.2		c.*2883G>A		3_prime_UTR	Exon 8 of 8	NP_001116827.1
	PPP6C	NM_001123369.2		c.*2883G>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.*2883G>A		3_prime_UTR	Exon 7 of 7	ENSP00000362648.4
	PPP6C	ENST00000451402.5	TSL:2	c.*2883G>A		3_prime_UTR	Exon 8 of 8	ENSP00000392147.1
	PPP6C	ENST00000415905.5	TSL:2	c.*2883G>A		3_prime_UTR	Exon 6 of 6	ENSP00000411744.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67160 AN: 151786 Hom.: 15219 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.441

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.443 AC: 67221 AN: 151904 Hom.: 15240 Cov.: 32 AF XY: 0.433 AC XY: 32184 AN XY: 74258

African (AFR) AF: 0.476 AC: 19704 AN: 41416

American (AMR) AF: 0.370 AC: 5646 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1746 AN: 3468

East Asian (EAS) AF: 0.529 AC: 2728 AN: 5154

South Asian (SAS) AF: 0.410 AC: 1972 AN: 4810

European-Finnish (FIN) AF: 0.294 AC: 3103 AN: 10554

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

European-Non Finnish (NFE) AF: 0.454 AC: 30830 AN: 67940

Other (OTH) AF: 0.448 AC: 943 AN: 2104

Alfa AF: 0.445 Hom.: 4144

Bravo AF: 0.451

Asia WGS AF: 0.495 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.8
DANN	Benign	0.76
PhyloP100		0.54
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: rs6744; hg19: chr9-127909069;