7-113918581-G-C

Variant names:

• chr7-113918581-G-C
• rs1057524893
• NM_002711.4:c.416C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_002711.4(PPP1R3A):​c.416C>G​(p.Ser139Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP1R3A NM_002711.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.68
• Publications: 0 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35609716).
• BP6: Variant 7-113918581-G-C is Benign according to our data. Variant chr7-113918581-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 393406.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R3A	NM_002711.4	MANE Select	c.416C>G	p.Ser139Cys	missense	Exon 1 of 4	NP_002702.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R3A	ENST00000284601.4	TSL:1 MANE Select	c.416C>G	p.Ser139Cys	missense	Exon 1 of 4	ENSP00000284601.3
	PPP1R3A	ENST00000284602.1	TSL:1	n.178+238C>G		intron	N/A	ENSP00000284602.1
	PPP1R3A	ENST00000449795.5	TSL:3	c.-181-36261C>G		intron	N/A	ENSP00000401278.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Monogenic diabetes Benign:1

Sep 09, 2016

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: research

ACMG Criteria: PM2, PP3, BP4, BP5

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.29
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.070	T
Polyphen		1.0	D
Vest4		0.21
MutPred		0.56		Loss of disorder (P = 0.0014)
MVP		0.87
MPC		0.065
ClinPred		0.64	D
GERP RS		3.3
PromoterAI		-0.0047	Neutral
Varity_R		0.16
gMVP		0.27
Mutation Taster		=81/19	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: rs1057524893; hg19: chr7-113558636;