7-113918369-G-T

Variant names:

• chr7-113918369-G-T
• rs141223649
• NM_002711.4:c.628C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002711.4(PPP1R3A):​c.628C>A​(p.Arg210Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 151,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: PPP1R3A NM_002711.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.42

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R3A	NM_002711.4	c.628C>A	p.Arg210Ser	missense_variant	Exon 1 of 4	ENST00000284601.4	NP_002702.2
PPP1R3A	XM_005250473.4	c.97-72C>A		intron_variant	Intron 1 of 4		XP_005250530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R3A	ENST00000284601.4	c.628C>A	p.Arg210Ser	missense_variant	Exon 1 of 4	1	NM_002711.4	ENSP00000284601.3
PPP1R3A	ENST00000284602.1	n.179-72C>A		intron_variant	Intron 1 of 4	1		ENSP00000284602.1
PPP1R3A	ENST00000449795.5	c.-181-36049C>A		intron_variant	Intron 1 of 3	3		ENSP00000401278.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151902 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151902 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74188

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.52
Sift	Benign	0.040	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.71		Loss of stability (P = 0.2444);
MVP		0.91
MPC		0.32
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.68
gMVP		0.78

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: rs141223649; hg19: chr7-113558424;