Variant 19-38256231-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033256.3(PPP1R14A):c.109G>A(p.Val37Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000214 in 1,400,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PPP1R14A
NM_033256.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25569025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R14A	NM_033256.3 link	c.109G>A	p.Val37Ile	missense_variant	Exon 1 of 4	ENST00000301242.9	NP_150281.1	Q96A00-1
PPP1R14A	NM_001243947.2 link	c.109G>A	p.Val37Ile	missense_variant	Exon 1 of 3		NP_001230876.1	Q96A00-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R14A	ENST00000301242.9 link	c.109G>A	p.Val37Ile	missense_variant	Exon 1 of 4	1	NM_033256.3	ENSP00000301242.3		Q96A00-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000652

AC:

AN:

153342

Hom.:

AF XY:

0.00

AC XY:

AN XY:

83492

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000162

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1400350

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

692294

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000276

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000576

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2023

The c.109G>A (p.V37I) alteration is located in exon 1 (coding exon 1) of the PPP1R14A gene. This alteration results from a G to A substitution at nucleotide position 109, causing the valine (V) at amino acid position 37 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

T;.;T;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.096

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.2

.;M;M;.

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.40

.;N;N;.

REVEL

Benign

0.19

Sift

Benign

0.078

.;T;T;.

Sift4G

Benign

0.071

T;T;T;T

Polyphen

0.97, 0.98

.;D;D;.

Vest4

0.26

MutPred

0.74

Loss of phosphorylation at Y41 (P = 0.103);Loss of phosphorylation at Y41 (P = 0.103);Loss of phosphorylation at Y41 (P = 0.103);Loss of phosphorylation at Y41 (P = 0.103);

MVP

0.092

MPC

2.5

ClinPred

0.65

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over