dbSNP rs1057524893: PPP1R3A:p.Ser139Phe (chr7-113918581-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002711.4(PPP1R3A):c.416C>T(p.Ser139Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S139C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PPP1R3A
NM_002711.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.68

Publications

0 publications found

Variant links:

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

PPP1R3A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38824755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R3A	NM_002711.4 link	c.416C>T	p.Ser139Phe	missense_variant	Exon 1 of 4	ENST00000284601.4	NP_002702.2	Q16821-1
PPP1R3A	XM_005250473.4 link	c.96+238C>T		intron_variant	Intron 1 of 4		XP_005250530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPP1R3A	ENST00000284601.4 link	c.416C>T	p.Ser139Phe	missense_variant	Exon 1 of 4	1	NM_002711.4	ENSP00000284601.3	Q16821-1
PPP1R3A	ENST00000284602.1 link	n.178+238C>T		intron_variant	Intron 1 of 4	1		ENSP00000284602.1	Q16821-2
PPP1R3A	ENST00000449795.5 link	c.-181-36261C>T		intron_variant	Intron 1 of 3	3		ENSP00000401278.1	C9JZB3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726894

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111540

Other (OTH)

AF:

0.0000166

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.80

M_CAP

Benign

0.036

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.4

PhyloP100

3.7

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.29

Sift

Uncertain

0.0050

Sift4G

Benign

0.066

Polyphen

0.99

Vest4

0.31

MutPred

0.54

Loss of disorder (P = 0.0031);

MVP

0.87

MPC

0.30

ClinPred

0.95

GERP RS

3.3

PromoterAI

0.0034

Neutral

(source)

Varity_R

0.20

gMVP

0.30

Mutation Taster

=79/21

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over