chr7-113918864-C-T

Variant names:

• chr7-113918864-C-T
• rs8192687
• NM_002711.4:c.133G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002711.4(PPP1R3A):​c.133G>A​(p.Gly45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00625 in 1,613,728 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (66 hom.)
• Consequence: PPP1R3A NM_002711.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.94
• Publications: 11 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0061822236).
• BP6: Variant 7-113918864-C-T is Benign according to our data. Variant chr7-113918864-C-T is described in ClinVar as Benign. ClinVar VariationId is 549524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 Unknown gene

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.133G>A	p.Gly45Ser	missense	Exon 1 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.133G>A	p.Gly45Ser	missense	Exon 1 of 4	ENSP00000284601.3	Q16821-1
	PPP1R3A	ENST00000284602.1	TSL:1	n.133G>A		non_coding_transcript_exon	Exon 1 of 5	ENSP00000284602.1	Q16821-2
	PPP1R3A	ENST00000449795.5	TSL:3	c.-181-36544G>A		intron	N/A	ENSP00000401278.1	C9JZB3

Frequencies

GnomAD3 genomes AF: 0.00592 AC: 900 AN: 152016 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00688

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.00716 AC: 1796 AN: 250724 AF XY: 0.00750

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0266

Gnomad NFE exome AF: 0.00754

Gnomad OTH exome AF: 0.00688

GnomAD4 exome AF: 0.00629 AC: 9188 AN: 1461594 Hom.: 66 Cov.: 31 AF XY: 0.00641 AC XY: 4659 AN XY: 727108

African (AFR) AF: 0.000837 AC: 28 AN: 33462

American (AMR) AF: 0.00159 AC: 71 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 60 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00886 AC: 764 AN: 86252

European-Finnish (FIN) AF: 0.0262 AC: 1402 AN: 53416

Middle Eastern (MID) AF: 0.00659 AC: 38 AN: 5766

European-Non Finnish (NFE) AF: 0.00585 AC: 6508 AN: 1111798

Other (OTH) AF: 0.00525 AC: 317 AN: 60384

GnomAD4 genome AF: 0.00592 AC: 900 AN: 152134 Hom.: 7 Cov.: 32 AF XY: 0.00682 AC XY: 507 AN XY: 74380

African (AFR) AF: 0.00106 AC: 44 AN: 41512

American (AMR) AF: 0.00223 AC: 34 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00932 AC: 45 AN: 4826

European-Finnish (FIN) AF: 0.0272 AC: 288 AN: 10598

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00688 AC: 468 AN: 67982

Other (OTH) AF: 0.00285 AC: 6 AN: 2106

Alfa AF: 0.00567 Hom.: 7

Bravo AF: 0.00341

TwinsUK AF: 0.00647 AC: 24

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00430 AC: 37

ExAC AF: 0.00703 AC: 854

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00524

EpiControl AF: 0.00640

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Monogenic diabetes (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.073
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.9
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.061
Sift	Benign	0.15	T
Sift4G	Benign	0.082	T
Polyphen		0.11	B
Vest4		0.11
MVP		0.46
MPC		0.049
ClinPred		0.015	T
GERP RS		5.3
PromoterAI		-0.0054	Neutral
Varity_R		0.057
gMVP		0.13
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs8192687; hg19: chr7-113558919; COSMIC: COSV52892253;