rs147428443

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033256.3(PPP1R14A):c.428G>A(p.Arg143Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000736 in 1,521,566 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R143G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

PPP1R14A
NM_033256.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.281

Publications

1 publications found

Variant links:

Genes affected

PPP1R14A (HGNC:14871): (protein phosphatase 1 regulatory inhibitor subunit 14A) The protein encoded by this gene belongs to the protein phosphatase 1 (PP1) inhibitor family. This protein is an inhibitor of smooth muscle myosin phosphatase, and has higher inhibitory activity when phosphorylated. Inhibition of myosin phosphatase leads to increased myosin phosphorylation and enhanced smooth muscle contraction. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Sep 2011]

PPP1R14A links:

SPINT2 (HGNC:11247): (serine peptidase inhibitor, Kunitz type 2) This gene encodes a transmembrane protein with two extracellular Kunitz domains that inhibits a variety of serine proteases. The protein inhibits HGF activator which prevents the formation of active hepatocyte growth factor. This gene is a putative tumor suppressor, and mutations in this gene result in congenital sodium diarrhea. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

SPINT2 Gene-Disease associations (from GenCC):

syndromic congenital sodium diarrhea
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
congenital secretory sodium diarrhea 3
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

SPINT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05456707).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033256.3. 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
	PPP1R14A	NM_033256.3	MANE Select	c.428G>A	p.Arg143Gln	missense	Exon 4 of 4	NP_150281.1	Q96A00-1
	PPP1R14A	NM_001243947.2		c.347G>A	p.Arg116Gln	missense	Exon 3 of 3	NP_001230876.1	Q96A00-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPP1R14A	ENST00000301242.9	TSL:1 MANE Select	c.428G>A	p.Arg143Gln	missense	Exon 4 of 4	ENSP00000301242.3	Q96A00-1
PPP1R14A	ENST00000347262.8	TSL:1	c.347G>A	p.Arg116Gln	missense	Exon 3 of 3	ENSP00000301243.3	Q96A00-2
PPP1R14A	ENST00000956130.1		c.416G>A	p.Arg139Gln	missense	Exon 4 of 4	ENSP00000626189.1

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000129

AC:

AN:

154846

AF XY:

0.000172

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.000301

GnomAD4 exome

AF:

0.0000716

AC:

AN:

1369506

Hom.:

Cov.:

AF XY:

0.0000794

AC XY:

AN XY:

679714

show subpopulations

African (AFR)

AF:

0.000183

AC:

AN:

27304

American (AMR)

AF:

0.00

AC:

AN:

24126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22962

East Asian (EAS)

AF:

0.0000301

AC:

AN:

33270

South Asian (SAS)

AF:

0.0000139

AC:

AN:

72156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5472

European-Non Finnish (NFE)

AF:

0.0000769

AC:

AN:

1079344

Other (OTH)

AF:

0.000142

AC:

AN:

56512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000149

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.83

M_CAP

Benign

0.0050

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

0.28

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.39

REVEL

Benign

0.021

Sift

Benign

0.074

Sift4G

Benign

0.22

Polyphen

0.27

Vest4

0.13

MVP

0.18

MPC

0.0053

ClinPred

0.062

GERP RS

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.053

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over