rs567665284

Variant names:

• chr19-38251373-G-A
• NM_033256.3:c.389C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-38251373-G-A
• chr19-38251373-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033256.3(PPP1R14A):​c.389C>T​(p.Ser130Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000284 in 1,407,510 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: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: PPP1R14A NM_033256.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46

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]

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]

ACMG classification

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=0.22415137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R14A	NM_033256.3	c.389C>T	p.Ser130Phe	missense_variant	Exon 4 of 4	ENST00000301242.9	NP_150281.1
PPP1R14A	NM_001243947.2	c.308C>T	p.Ser103Phe	missense_variant	Exon 3 of 3		NP_001230876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R14A	ENST00000301242.9	c.389C>T	p.Ser130Phe	missense_variant	Exon 4 of 4	1	NM_033256.3	ENSP00000301242.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000284 AC: 4 AN: 1407510 Hom.: 0 Cov.: 32 AF XY: 0.00000428 AC XY: 3 AN XY: 700384

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: 0.00000366

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T;.;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.2	.;.;M
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.7	.;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0050	.;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.99, 1.0	.;D;D
Vest4		0.40
MutPred		0.32		.;.;Loss of phosphorylation at S130 (P = 0.0107);
MVP		0.20
MPC		0.022
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.19
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-38742013;