6-150143237-C-A

Position:

• chr6-150143237-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030949.3(PPP1R14C):​c.45C>A​(p.Ser15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP1R14C NM_030949.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.02

Genes affected

PPP1R14C (HGNC:14952): (protein phosphatase 1 regulatory inhibitor subunit 14C) The degree of protein phosphorylation is regulated by a balance of protein kinase and phosphatase activities. Protein phosphatase-1 (PP1; see MIM 176875) is a signal-transducing phosphatase that influences neuronal activity, protein synthesis, metabolism, muscle contraction, and cell division. PPP1R14C is an inhibitor of PP1 (Liu et al., 2002 [PubMed 11812771]).[supplied by OMIM, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093330085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R14C	NM_030949.3	c.45C>A	p.Ser15Arg	missense_variant	1/4	ENST00000361131.5	NP_112211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R14C	ENST00000361131.5	c.45C>A	p.Ser15Arg	missense_variant	1/4	1	NM_030949.3	ENSP00000355260.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1226612 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 598200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.45C>A (p.S15R) alteration is located in exon 1 (coding exon 1) of the PPP1R14C gene. This alteration results from a C to A substitution at nucleotide position 45, causing the serine (S) at amino acid position 15 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.1
DANN	Benign	0.81
DEOGEN2	Benign	0.067	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.021
Sift	Benign	0.068	T
Sift4G	Benign	0.10	T
Polyphen		0.016	B
Vest4		0.22
MutPred		0.33		Gain of methylation at S15 (P = 0.0022);
MVP		0.27
MPC		0.68
ClinPred		0.11	T
GERP RS		-2.1
Varity_R		0.058
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-150464373;