12-110720356-T-C

Variant summary

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

The NM_002710.4(PPP1CC):c.*720A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 636,068 control chromosomes in the GnomAD database, including 6,469 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 0.17 (3092 hom., cov: 32)
  • Exomes 𝑓: 0.10 (3377 hom.)
• Consequence: PPP1CC NM_002710.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

Genes affected

PPP1CC (HGNC:9283): (protein phosphatase 1 catalytic subunit gamma) The protein encoded by this gene belongs to the protein phosphatase family, PP1 subfamily. PP1 is an ubiquitous serine/threonine phosphatase that regulates many cellular processes, including cell division. It is expressed in mammalian cells as three closely related isoforms, alpha, beta/delta and gamma, which have distinct localization patterns. This gene encodes the gamma isozyme. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1CC	NM_002710.4	c.*720A>G		3_prime_UTR_variant	7/7	ENST00000335007.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1CC	ENST00000335007.10	c.*720A>G		3_prime_UTR_variant	7/7	1	NM_002710.4	P1
PPP1CC	ENST00000340766.9	c.944-152A>G		intron_variant		2
PPP1CC	ENST00000550261.5	c.*363-152A>G		intron_variant, NMD_transcript_variant		5
PPP1CC	ENST00000546904.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25142 AN: 152064 Hom.: 3076 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0989

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0738

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.105 AC: 50777 AN: 483886 Hom.: 3377 Cov.: 6 AF XY: 0.105 AC XY: 27083 AN XY: 257764

Gnomad4 AFR exome AF: 0.360

Gnomad4 AMR exome AF: 0.0813

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.00451

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.0715

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.166 AC: 25192 AN: 152182 Hom.: 3092 Cov.: 32 AF XY: 0.161 AC XY: 11957 AN XY: 74412

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.0985

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.00520

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0738

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.148

Alfa AF: 0.120 Hom.: 513

Bravo AF: 0.175

Asia WGS AF: 0.0830 AC: 291 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	6.7
Dann	Benign	0.68

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

LitVar

Other links and lift over

dbSNP: rs1050587; hg19: chr12-111158161;