14-23297382-G-A

Variant names:

• chr14-23297382-G-A
• rs1884056
• NM_001276318.2:c.*1922C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276318.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R3E	NM_001276318.2	MANE Select	c.*1922C>T		3_prime_UTR	Exon 5 of 5	NP_001263247.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R3E	ENST00000452015.9	TSL:2 MANE Select	c.*1922C>T		3_prime_UTR	Exon 5 of 5	ENSP00000408288.3
	PPP1R3E	ENST00000558058.5	TSL:3	c.*1727C>T		3_prime_UTR	Exon 4 of 4	ENSP00000453175.1
	PPP1R3E	ENST00000559314.5	TSL:2	c.*1242C>T		3_prime_UTR	Exon 5 of 5	ENSP00000454106.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.348 AC: 16 AN: 46

Other (OTH) AF: 0.00 AC: 0 AN: 6

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

African (AFR) AF: 0.0925 AC: 3839 AN: 41514

American (AMR) AF: 0.326 AC: 4970 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1207 AN: 3468

East Asian (EAS) AF: 0.495 AC: 2554 AN: 5164

South Asian (SAS) AF: 0.277 AC: 1335 AN: 4822

European-Finnish (FIN) AF: 0.343 AC: 3626 AN: 10584

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21534 AN: 67962

Other (OTH) AF: 0.266 AC: 561 AN: 2106

Alfa AF: 0.304 Hom.: 33336

Bravo AF: 0.261

Asia WGS AF: 0.299 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.54
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1884056; hg19: chr14-23766591;