rs1884056

Positions:

• chr14-23297382-G-A
• chr14-23297382-G-T

Variant summary

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

The NM_001276318.2(PPP1R3E):​c.*1922C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,152 control chromosomes in the GnomAD database, including 6,323 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 0.26 (6318 hom., cov: 32)
  • Exomes 𝑓: 0.35 (5 hom.)
• Consequence: PPP1R3E NM_001276318.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

Genes affected

PPP1R3E (HGNC:14943): (protein phosphatase 1 regulatory subunit 3E) Predicted to enable [phosphorylase] phosphatase activity; glycogen binding activity; and protein phosphatase 1 binding activity. Predicted to be involved in positive regulation of glycogen biosynthetic process. Predicted to be located in glycogen granule. Predicted to be part of protein phosphatase type 1 complex. [provided by Alliance of Genome Resources, Apr 2022]

HOMEZ (HGNC:20164): (homeobox and leucine zipper encoding) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R3E	NM_001276318.2	c.*1922C>T		3_prime_UTR_variant	5/5	ENST00000452015.9	NP_001263247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R3E	ENST00000452015	c.*1922C>T		3_prime_UTR_variant	5/5	2	NM_001276318.2	ENSP00000408288.3
PPP1R3E	ENST00000558058.5	c.*1727C>T		3_prime_UTR_variant	4/4	3		ENSP00000453175.1
PPP1R3E	ENST00000559314.5	c.*1242C>T		3_prime_UTR_variant	5/5	2		ENSP00000454106.1
HOMEZ	ENST00000561013.3	c.-113+2019C>T		intron_variant		2		ENSP00000453979.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40283 AN: 151974 Hom.: 6321 Cov.: 32

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.350 AC: 21 AN: 60 Hom.: 5 Cov.: 0 AF XY: 0.396 AC XY: 19 AN XY: 48

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.348

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.265 AC: 40283 AN: 152092 Hom.: 6318 Cov.: 32 AF XY: 0.270 AC XY: 20100 AN XY: 74352

Gnomad4 AFR AF: 0.0925

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.266

Alfa AF: 0.311 Hom.: 15692

Bravo AF: 0.261

Asia WGS AF: 0.299 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs1884056; hg19: chr14-23766591;