7-113878300-G-T

Position:

• chr7-113878300-G-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PS1_Moderate BP4_Strong BP6 BS2

The NM_002711.4(PPP1R3A):​c.2792C>A​(p.Ala931Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,613,136 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (2 hom.)
• Consequence: PPP1R3A NM_002711.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454

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 Benign. Variant got -7 ACMG points.

• PS1: Transcript NM_002711.4 (PPP1R3A) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
• BP4: Computational evidence support a benign effect (MetaRNN=0.0057417452).
• BP6: Variant 7-113878300-G-T is Benign according to our data. Variant chr7-113878300-G-T is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome4 at 2 Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R3A	NM_002711.4	c.2792C>A	p.Ala931Glu	missense_variant	4/4	ENST00000284601.4	NP_002702.2
PPP1R3A	XM_005250473.4	c.2189C>A	p.Ala730Glu	missense_variant	5/5		XP_005250530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R3A	ENST00000284601.4	c.2792C>A	p.Ala931Glu	missense_variant	4/4	1	NM_002711.4	ENSP00000284601.3

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 237 AN: 151970 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.00136 AC: 339 AN: 249668 Hom.: 0 AF XY: 0.00142 AC XY: 191 AN XY: 134948

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00134

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.00225

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00193 AC: 2816 AN: 1461048 Hom.: 2 Cov.: 31 AF XY: 0.00188 AC XY: 1367 AN XY: 726856

Gnomad4 AFR exome AF: 0.000688

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.000958

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.0000940

Gnomad4 NFE exome AF: 0.00230

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.00155 AC: 235 AN: 152088 Hom.: 0 Cov.: 32 AF XY: 0.00143 AC XY: 106 AN XY: 74342

Gnomad4 AFR AF: 0.000674

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00256

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00231 Hom.: 2

Bravo AF: 0.00155

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00198 AC: 17

ExAC AF: 0.00119 AC: 145

Asia WGS AF: 0.000289 AC: 1 AN: 3476

EpiCase AF: 0.00278

EpiControl AF: 0.00296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.2
DANN	Benign	0.46
DEOGEN2	Benign	0.087	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.76	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.017
Sift	Benign	0.33	T
Sift4G	Benign	0.96	T
Polyphen		0.0010	B
Vest4		0.063
MVP		0.18
MPC		0.049
ClinPred		0.0068	T
GERP RS		1.9
Varity_R		0.063
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs35449651; hg19: chr7-113518355; COSMIC: COSV52877647; COSMIC: COSV52877647;