12-110742702-C-G

Variant names:

• chr12-110742702-C-G
• rs367543177
• NM_002710.4:c.6G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_002710.4(PPP1CC):​c.6G>C​(p.Ala2Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000767 in 1,303,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A2A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: PPP1CC NM_002710.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.01
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BP7: Synonymous conserved (PhyloP=3.01 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CC	NM_002710.4	MANE Select	c.6G>C	p.Ala2Ala	synonymous	Exon 1 of 7	NP_002701.1	P36873-1
	PPP1CC	NM_001244974.2		c.6G>C	p.Ala2Ala	synonymous	Exon 1 of 8	NP_001231903.1	P36873-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CC	ENST00000335007.10	TSL:1 MANE Select	c.6G>C	p.Ala2Ala	synonymous	Exon 1 of 7	ENSP00000335084.5	P36873-1
	PPP1CC	ENST00000340766.9	TSL:2	c.6G>C	p.Ala2Ala	synonymous	Exon 1 of 8	ENSP00000341779.5	P36873-2
	PPP1CC	ENST00000550991.5	TSL:2	c.6G>C	p.Ala2Ala	synonymous	Exon 1 of 6	ENSP00000448981.1	F8VYE8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.67e-7 AC: 1 AN: 1303708 Hom.: 0 Cov.: 35 AF XY: 0.00000155 AC XY: 1 AN XY: 644024

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27694

American (AMR) AF: 0.00 AC: 0 AN: 30306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21870

East Asian (EAS) AF: 0.00 AC: 0 AN: 31082

South Asian (SAS) AF: 0.00 AC: 0 AN: 63348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5210

European-Non Finnish (NFE) AF: 9.76e-7 AC: 1 AN: 1025094

Other (OTH) AF: 0.00 AC: 0 AN: 52164

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	17
DANN	Benign	0.91
PhyloP100		3.0
PromoterAI		-0.079	Neutral

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: rs367543177; hg19: chr12-111180507;