rs1800000

Variant names:

• chr7-113878443-C-A
• rs1800000
• NM_002711.4:c.2649G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-113878443-C-A
• chr7-113878443-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002711.4(PPP1R3A):​c.2649G>T​(p.Arg883Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,612,206 control chromosomes in the GnomAD database, including 825 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 ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (111 hom., cov: 32)
  • Exomes 𝑓: 0.012 (714 hom.)
• Consequence: PPP1R3A NM_002711.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.891
• Publications: 18 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.697574E-4).
• BP6: Variant 7-113878443-C-A is Benign according to our data. Variant chr7-113878443-C-A is described in ClinVar as Benign. ClinVar VariationId is 549519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

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.2649G>T	p.Arg883Ser	missense	Exon 4 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.2649G>T	p.Arg883Ser	missense	Exon 4 of 4	ENSP00000284601.3

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2630 AN: 151958 Hom.: 111 Cov.: 32

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0372

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00421

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.0319 AC: 7947 AN: 249312 AF XY: 0.0278

Gnomad AFR exome AF: 0.00284

Gnomad AMR exome AF: 0.0727

Gnomad ASJ exome AF: 0.0122

Gnomad EAS exome AF: 0.144

Gnomad FIN exome AF: 0.0830

Gnomad NFE exome AF: 0.00549

Gnomad OTH exome AF: 0.0247

GnomAD4 exome AF: 0.0117 AC: 17126 AN: 1460130 Hom.: 714 Cov.: 33 AF XY: 0.0112 AC XY: 8120 AN XY: 726430

African (AFR) AF: 0.00188 AC: 63 AN: 33444

American (AMR) AF: 0.0696 AC: 3106 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.0120 AC: 313 AN: 26116

East Asian (EAS) AF: 0.132 AC: 5255 AN: 39670

South Asian (SAS) AF: 0.00481 AC: 415 AN: 86242

European-Finnish (FIN) AF: 0.0774 AC: 4046 AN: 52242

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5766

European-Non Finnish (NFE) AF: 0.00273 AC: 3030 AN: 1111706

Other (OTH) AF: 0.0147 AC: 887 AN: 60348

GnomAD4 genome AF: 0.0173 AC: 2633 AN: 152076 Hom.: 111 Cov.: 32 AF XY: 0.0217 AC XY: 1610 AN XY: 74342

African (AFR) AF: 0.00251 AC: 104 AN: 41514

American (AMR) AF: 0.0374 AC: 570 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3470

East Asian (EAS) AF: 0.135 AC: 697 AN: 5148

South Asian (SAS) AF: 0.00560 AC: 27 AN: 4824

European-Finnish (FIN) AF: 0.0824 AC: 874 AN: 10608

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00421 AC: 286 AN: 67946

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.00979 Hom.: 217

Bravo AF: 0.0161

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.00326 AC: 28

ExAC AF: 0.0283 AC: 3437

Asia WGS AF: 0.0520 AC: 180 AN: 3474

EpiCase AF: 0.00235

EpiControl AF: 0.00296

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Monogenic diabetes (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.034
DANN	Benign	0.38
DEOGEN2	Benign	0.060	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.00037	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.89
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.60	N
REVEL	Benign	0.016
Sift	Benign	0.26	T
Sift4G	Benign	0.76	T
Polyphen		0.0050	B
Vest4		0.029
MutPred		0.17		Gain of phosphorylation at R883 (P = 0.0209)
MPC		0.048
ClinPred		0.0026	T
GERP RS		-3.9
Varity_R		0.071
gMVP		0.069
Mutation Taster		=99/1	polymorphism (auto)

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: rs1800000; hg19: chr7-113518498; COSMIC: COSV52878887; COSMIC: COSV52878887;