rs3758644

Positions:

• chr11-68598620-C-T

Variant summary

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

The NM_001164161.2(PPP6R3):​c.2039-1721C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 152,258 control chromosomes in the GnomAD database, including 256 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 0.056 (256 hom., cov: 32)
• Consequence: PPP6R3 NM_001164161.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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]

PPP6R3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP6R3	NM_001164161.2	c.2039-1721C>T		intron_variant		ENST00000393800.7	NP_001157633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP6R3	ENST00000393800.7	c.2039-1721C>T		intron_variant		1	NM_001164161.2	ENSP00000377389.2

Frequencies

GnomAD3 genomes AF: 0.0563 AC: 8562 AN: 152140 Hom.: 254 Cov.: 32

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.00884

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0563 AC: 8571 AN: 152258 Hom.: 256 Cov.: 32 AF XY: 0.0540 AC XY: 4020 AN XY: 74446

Gnomad4 AFR AF: 0.0513

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.0877

Gnomad4 EAS AF: 0.00886

Gnomad4 SAS AF: 0.0342

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.0681

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0630 Hom.: 45

Bravo AF: 0.0601

Asia WGS AF: 0.0390 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.80

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: rs3758644; hg19: chr11-68366088;