chr12-110722198-G-A

Variant names:

• chr12-110722198-G-A
• rs1973505
• NM_002710.4:c.819C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002710.4(PPP1CC):​c.819C>T​(p.Cys273Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,613,756 control chromosomes in the GnomAD database, including 23,905 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 0.23 (6022 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17883 hom.)
• Consequence: PPP1CC NM_002710.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99
• Publications: 20 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=2.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CC	NM_002710.4	c.819C>T	p.Cys273Cys	synonymous_variant	Exon 6 of 7	ENST00000335007.10	NP_002701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CC	ENST00000335007.10	c.819C>T	p.Cys273Cys	synonymous_variant	Exon 6 of 7	1	NM_002710.4	ENSP00000335084.5
PPP1CC	ENST00000550261.5	n.*238C>T		non_coding_transcript_exon_variant	Exon 3 of 5	5		ENSP00000447528.2
PPP1CC	ENST00000550261.5	n.*238C>T		3_prime_UTR_variant	Exon 3 of 5	5		ENSP00000447528.2

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35142 AN: 151950 Hom.: 6005 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0730

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.208

GnomAD2 exomes AF: 0.149 AC: 37559 AN: 251334 AF XY: 0.147

Gnomad AFR exome AF: 0.498

Gnomad AMR exome AF: 0.0915

Gnomad ASJ exome AF: 0.176

Gnomad EAS exome AF: 0.0681

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.142 AC: 208265 AN: 1461688 Hom.: 17883 Cov.: 32 AF XY: 0.142 AC XY: 103420 AN XY: 727136

African (AFR) AF: 0.511 AC: 17092 AN: 33470

American (AMR) AF: 0.0961 AC: 4299 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 4483 AN: 26132

East Asian (EAS) AF: 0.0614 AC: 2436 AN: 39694

South Asian (SAS) AF: 0.164 AC: 14158 AN: 86224

European-Finnish (FIN) AF: 0.105 AC: 5617 AN: 53414

Middle Eastern (MID) AF: 0.204 AC: 1176 AN: 5768

European-Non Finnish (NFE) AF: 0.134 AC: 149294 AN: 1111888

Other (OTH) AF: 0.161 AC: 9710 AN: 60384

GnomAD4 genome AF: 0.231 AC: 35197 AN: 152068 Hom.: 6022 Cov.: 32 AF XY: 0.226 AC XY: 16816 AN XY: 74338

African (AFR) AF: 0.493 AC: 20409 AN: 41436

American (AMR) AF: 0.132 AC: 2025 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 602 AN: 3470

East Asian (EAS) AF: 0.0732 AC: 379 AN: 5180

South Asian (SAS) AF: 0.168 AC: 812 AN: 4830

European-Finnish (FIN) AF: 0.110 AC: 1164 AN: 10566

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9173 AN: 67984

Other (OTH) AF: 0.207 AC: 437 AN: 2110

Alfa AF: 0.174 Hom.: 2936

Bravo AF: 0.246

Asia WGS AF: 0.150 AC: 524 AN: 3478

EpiCase AF: 0.142

EpiControl AF: 0.147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	10
DANN	Benign	0.63
PhyloP100		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=87/13	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: rs1973505; hg19: chr12-111160003; COSMIC: COSV58583488;