7-113877754-C-T

Position:

• chr7-113877754-C-T

Variant summary

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

The NM_002711.4(PPP1R3A):​c.3338G>A​(p.Gly1113Asp) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP1R3A NM_002711.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.87

Genes affected

PPP1R3A (HGNC:9291): (protein phosphatase 1 regulatory subunit 3A) The glycogen-associated form of protein phosphatase-1 (PP1) derived from skeletal muscle is a heterodimer composed of a 37-kD catalytic subunit and a 124-kD targeting and regulatory subunit. This gene encodes the regulatory subunit which binds to muscle glycogen with high affinity, thereby enhancing dephosphorylation of glycogen-bound substrates for PP1 such as glycogen synthase and glycogen phosphorylase kinase. [provided by RefSeq, Jul 2008]

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=0.22163138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R3A	NM_002711.4	c.3338G>A	p.Gly1113Asp	missense_variant	4/4	ENST00000284601.4	NP_002702.2
PPP1R3A	XM_005250473.4	c.2735G>A	p.Gly912Asp	missense_variant	5/5		XP_005250530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R3A	ENST00000284601.4	c.3338G>A	p.Gly1113Asp	missense_variant	4/4	1	NM_002711.4	ENSP00000284601	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Mar 20, 2024

The c.3338G>A (p.G1113D) alteration is located in exon 4 (coding exon 4) of the PPP1R3A gene. This alteration results from a G to A substitution at nucleotide position 3338, causing the glycine (G) at amino acid position 1113 to be replaced by an aspartic acid (D). 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	0.19
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	0.87	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.097
Sift	Benign	0.055	T
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.14
MutPred		0.28		Loss of MoRF binding (P = 0.0731);
MVP		0.50
MPC		0.30
ClinPred		0.93	D
GERP RS		5.0
Varity_R		0.16
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1796592898; hg19: chr7-113517809;