7-113879268-G-C

Variant names:

• chr7-113879268-G-C
• rs767098711
• NM_002711.4:c.1824C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002711.4(PPP1R3A):​c.1824C>G​(p.Ser608Arg) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP1R3A NM_002711.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 1 publications found

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]

PPP1R3A Gene-Disease associations (from GenCC):

• diabetes mellitus, noninsulin-dependent

  Inheritance: Unknown Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06491262).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002711.4. 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
	PPP1R3A	NM_002711.4	MANE Select	c.1824C>G	p.Ser608Arg	missense	Exon 4 of 4	NP_002702.2	Q16821-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R3A	ENST00000284601.4	TSL:1 MANE Select	c.1824C>G	p.Ser608Arg	missense	Exon 4 of 4	ENSP00000284601.3	Q16821-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.065
DANN	Benign	0.86
DEOGEN2	Benign	0.065	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.1
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.049
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.42	T
Polyphen		0.39	B
Vest4		0.066
MutPred		0.28		Loss of glycosylation at S608 (P = 0.0218)
MVP		0.24
MPC		0.060
ClinPred		0.19	T
GERP RS		-12
Varity_R		0.094
gMVP		0.14
Mutation Taster		=98/2	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: rs767098711; hg19: chr7-113519323;