rs12610267

Positions:

• chr19-38254093-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033256.3(PPP1R14A):​c.202-1119T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,028 control chromosomes in the GnomAD database, including 17,774 homozygotes. 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: 𝑓 0.47 (17774 hom., cov: 32)
• Consequence: PPP1R14A NM_033256.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R14A	NM_033256.3	c.202-1119T>C		intron_variant		ENST00000301242.9	NP_150281.1
PPP1R14A	NM_001243947.2	c.202-1755T>C		intron_variant			NP_001230876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R14A	ENST00000301242.9	c.202-1119T>C		intron_variant		1	NM_033256.3	ENSP00000301242.3

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71100 AN: 151910 Hom.: 17744 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.435

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.468 AC: 71195 AN: 152028 Hom.: 17774 Cov.: 32 AF XY: 0.480 AC XY: 35638 AN XY: 74312

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.439

Alfa AF: 0.489 Hom.: 20323

Bravo AF: 0.456

Asia WGS AF: 0.653 AC: 2267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.9
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs12610267; hg19: chr19-38744733;