12-110720356-T-C

Variant names:

• chr12-110720356-T-C
• rs1050587
• NM_002710.4:c.*720A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002710.4. 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
	PPP1CC	NM_002710.4	MANE Select	c.*720A>G		3_prime_UTR	Exon 7 of 7	NP_002701.1
	PPP1CC	NM_001244974.2		c.944-152A>G		intron	N/A	NP_001231903.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CC	ENST00000335007.10	TSL:1 MANE Select	c.*720A>G		3_prime_UTR	Exon 7 of 7	ENSP00000335084.5
	PPP1CC	ENST00000550261.5	TSL:5	n.*363-152A>G		intron	N/A	ENSP00000447528.2
	PPP1CC	ENST00000340766.9	TSL:2	c.944-152A>G		intron	N/A	ENSP00000341779.5

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

African (AFR) AF: 0.360 AC: 4762 AN: 13232

American (AMR) AF: 0.0813 AC: 1685 AN: 20722

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 2150 AN: 14648

East Asian (EAS) AF: 0.00451 AC: 140 AN: 31030

South Asian (SAS) AF: 0.114 AC: 5266 AN: 46180

European-Finnish (FIN) AF: 0.0715 AC: 2100 AN: 29362

Middle Eastern (MID) AF: 0.134 AC: 272 AN: 2030

European-Non Finnish (NFE) AF: 0.104 AC: 31027 AN: 299284

Other (OTH) AF: 0.123 AC: 3375 AN: 27398

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

African (AFR) AF: 0.350 AC: 14503 AN: 41450

American (AMR) AF: 0.0985 AC: 1507 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3470

East Asian (EAS) AF: 0.00520 AC: 27 AN: 5190

South Asian (SAS) AF: 0.115 AC: 555 AN: 4828

European-Finnish (FIN) AF: 0.0738 AC: 782 AN: 10596

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6867 AN: 68032

Other (OTH) AF: 0.148 AC: 312 AN: 2112

Alfa AF: 0.126 Hom.: 699

Bravo AF: 0.175

Asia WGS AF: 0.0830 AC: 291 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.7
DANN	Benign	0.68
PhyloP100		-0.025
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: rs1050587; hg19: chr12-111158161;