chr7-113878101-G-C

Position:

• chr7-113878101-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002711.4(PPP1R3A):​c.2991C>G​(p.Phe997Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F997C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP1R3A NM_002711.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.579

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059159547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R3A	NM_002711.4	c.2991C>G	p.Phe997Leu	missense_variant	4/4	ENST00000284601.4	NP_002702.2
PPP1R3A	XM_005250473.4	c.2388C>G	p.Phe796Leu	missense_variant	5/5		XP_005250530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R3A	ENST00000284601.4	c.2991C>G	p.Phe997Leu	missense_variant	4/4	1	NM_002711.4	ENSP00000284601	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Mar 25, 2024

The c.2991C>G (p.F997L) alteration is located in exon 4 (coding exon 4) of the PPP1R3A gene. This alteration results from a C to G substitution at nucleotide position 2991, causing the phenylalanine (F) at amino acid position 997 to be replaced by a leucine (L). 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	Uncertain	0.55
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.3
DANN	Benign	0.51
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.038
Sift	Benign	0.72	T
Sift4G	Benign	0.84	T
Polyphen		0.0020	B
Vest4		0.052
MutPred		0.28		Gain of catalytic residue at F997 (P = 0.0471);
MVP		0.18
MPC		0.049
ClinPred		0.026	T
GERP RS		1.2
Varity_R		0.058
gMVP		0.25

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: chr7-113518156;