rs4316515

Variant names:

• chr11-68541372-A-T
• rs4316515
• NM_001164161.2:c.228-3466A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164161.2(PPP6R3):​c.228-3466A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,078 control chromosomes in the GnomAD database, including 4,278 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 0.23 (4278 hom., cov: 32)
• Consequence: PPP6R3 NM_001164161.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.763
• Publications: 6 publications found

Genes affected

PPP6R3 (HGNC:1173): (protein phosphatase 6 regulatory subunit 3) Protein phosphatase regulatory subunits, such as SAPS3, modulate the activity of protein phosphatase catalytic subunits by restricting substrate specificity, recruiting substrates, and determining the intracellular localization of the holoenzyme. SAPS3 is a regulatory subunit for the protein phosphatase-6 catalytic subunit (PPP6C; MIM 612725) (Stefansson and Brautigan, 2006 [PubMed 16769727]).[supplied by OMIM, Nov 2010]

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 (AMR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP6R3	NM_001164161.2	c.228-3466A>T		intron_variant	Intron 3 of 23	ENST00000393800.7	NP_001157633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP6R3	ENST00000393800.7	c.228-3466A>T		intron_variant	Intron 3 of 23	1	NM_001164161.2	ENSP00000377389.2

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34976 AN: 151958 Hom.: 4276 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.230 AC: 34987 AN: 152078 Hom.: 4278 Cov.: 32 AF XY: 0.224 AC XY: 16653 AN XY: 74352

African (AFR) AF: 0.202 AC: 8394 AN: 41454

American (AMR) AF: 0.252 AC: 3860 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1161 AN: 5168

South Asian (SAS) AF: 0.166 AC: 802 AN: 4826

European-Finnish (FIN) AF: 0.165 AC: 1750 AN: 10584

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.252 AC: 17149 AN: 67978

Other (OTH) AF: 0.266 AC: 560 AN: 2106

Alfa AF: 0.229 Hom.: 514

Bravo AF: 0.242

Asia WGS AF: 0.193 AC: 671 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	9.7
DANN	Benign	0.79
PhyloP100		0.76
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: rs4316515; hg19: chr11-68308840;