NM_002709.3:c.30C>T

Variant names:

• chr2-28752154-C-T
• rs1404169743
• NM_002709.3:c.30C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_002709.3(PPP1CB):​c.30C>T​(p.Ser10Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000071 in 1,548,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: PPP1CB NM_002709.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.589
• Publications: 0 publications found

Genes affected

PPP1CB (HGNC:9282): (protein phosphatase 1 catalytic subunit beta) The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Mouse studies suggest that PP1 functions as a suppressor of learning and memory. Two alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

PPP1CB Gene-Disease associations (from GenCC):

• Noonan syndrome-like disorder with loose anagen hair

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Noonan syndrome-like disorder with loose anagen hair 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• cardiofaciocutaneous syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Costello syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome with multiple lentigines

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 2-28752154-C-T is Benign according to our data. Variant chr2-28752154-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1727612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.589 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002709.3. 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
	PPP1CB	NM_002709.3	MANE Select	c.30C>T	p.Ser10Ser	synonymous	Exon 1 of 8	NP_002700.1	P62140
	PPP1CB	NM_206876.2		c.30C>T	p.Ser10Ser	synonymous	Exon 2 of 9	NP_996759.1	P62140

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CB	ENST00000395366.3	TSL:1 MANE Select	c.30C>T	p.Ser10Ser	synonymous	Exon 1 of 8	ENSP00000378769.2	P62140
	PPP1CB	ENST00000296122.10	TSL:1	c.30C>T	p.Ser10Ser	synonymous	Exon 2 of 9	ENSP00000296122.6	P62140
	PPP1CB	ENST00000703174.1		c.30C>T	p.Ser10Ser	synonymous	Exon 1 of 9	ENSP00000515220.1	A0A8V8TRH9

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152106 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000676 AC: 1 AN: 147884 AF XY: 0.0000128

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000716 AC: 10 AN: 1396240 Hom.: 0 Cov.: 31 AF XY: 0.00000871 AC XY: 6 AN XY: 688684

African (AFR) AF: 0.00 AC: 0 AN: 31070

American (AMR) AF: 0.00 AC: 0 AN: 35626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25084

East Asian (EAS) AF: 0.00 AC: 0 AN: 35256

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 0.00000650 AC: 7 AN: 1077512

Other (OTH) AF: 0.0000173 AC: 1 AN: 57878

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152106 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74294

African (AFR) AF: 0.0000241 AC: 1 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cardiovascular phenotype (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	13
DANN	Benign	0.96
PhyloP100		0.59
PromoterAI		-0.062	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.9
Mutation Taster		=92/8	polymorphism

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: rs1404169743; hg19: chr2-28975020;