dbSNP rs1166839796: PPP1R14A:p.Val37Leu (chr19-38256231-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_033256.3(PPP1R14A):c.109G>C(p.Val37Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000357 in 1,400,350 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

PPP1R14A
NM_033256.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.289764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R14A	NM_033256.3 link	c.109G>C	p.Val37Leu	missense_variant	Exon 1 of 4	ENST00000301242.9	NP_150281.1	Q96A00-1
PPP1R14A	NM_001243947.2 link	c.109G>C	p.Val37Leu	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>C	p.Val37Leu	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:

0.0000120

AC XY:

AN XY:

83492

show subpopulations

Gnomad AFR exome

AF:

0.000117

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000357

AC:

AN:

1400350

Hom.:

Cov.:

AF XY:

0.00000289

AC XY:

AN XY:

692294

show subpopulations

Gnomad4 AFR exome

AF:

0.000155

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.038

T;.;T;.

Eigen

Benign

0.10

Eigen_PC

Benign

0.064

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

.;L;L;.

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-1.3

.;N;N;.

REVEL

Uncertain

0.46

Sift

Benign

0.38

.;T;T;.

Sift4G

Benign

0.088

T;T;T;T

Polyphen

0.98, 0.98

.;D;D;.

Vest4

0.46

MutPred

0.74

Loss of methylation at K40 (P = 0.0665);Loss of methylation at K40 (P = 0.0665);Loss of methylation at K40 (P = 0.0665);Loss of methylation at K40 (P = 0.0665);

MVP

0.085

MPC

2.7

ClinPred

0.42

GERP RS

3.4

Varity_R

0.26

gMVP

0.75

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over