rs11558238

Variant names:

• chr12-110721078-A-T
• rs11558238
• NM_002710.4:c.970T>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_002710.4(PPP1CC):​c.970T>A​(p.Ter324Lysext*?) variant causes a stop lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP1CC NM_002710.4 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.26

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_002710.4 Downstream stopcodon found after 66 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CC	NM_002710.4	c.970T>A	p.Ter324Lysext*?	stop_lost	Exon 7 of 7	ENST00000335007.10	NP_002701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CC	ENST00000335007.10	c.970T>A	p.Ter324Lysext*?	stop_lost	Exon 7 of 7	1	NM_002710.4	ENSP00000335084.5
PPP1CC	ENST00000550261.5	n.*362+27T>A		intron_variant	Intron 4 of 4	5		ENSP00000447528.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.50
DEOGEN2	Benign	0.022	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.25	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.44	T
REVEL	Pathogenic	0.66
Sift4G	Uncertain	0.0050	D
MVP		0.90
ClinPred		0.49	T
GERP RS		5.8

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: rs11558238; hg19: chr12-111158883;