rs3758644

Variant names:

• chr11-68598620-C-T
• rs3758644
• NM_001164161.2:c.2039-1721C>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.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
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164161.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP6R3	NM_001164161.2	MANE Select	c.2039-1721C>T		intron	N/A	NP_001157633.1	Q5H9R7-1
	PPP6R3	NM_001352354.2		c.2039-1721C>T		intron	N/A	NP_001339283.1
	PPP6R3	NM_001352356.2		c.2039-1721C>T		intron	N/A	NP_001339285.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP6R3	ENST00000393800.7	TSL:1 MANE Select	c.2039-1721C>T		intron	N/A	ENSP00000377389.2	Q5H9R7-1
	PPP6R3	ENST00000393801.7	TSL:1	c.2039-1721C>T		intron	N/A	ENSP00000377390.3	Q5H9R7-5
	PPP6R3	ENST00000524904.5	TSL:1	c.2021-1721C>T		intron	N/A	ENSP00000433058.1	Q5H9R7-2

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

African (AFR) AF: 0.0513 AC: 2130 AN: 41554

American (AMR) AF: 0.0559 AC: 855 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0877 AC: 304 AN: 3468

East Asian (EAS) AF: 0.00886 AC: 46 AN: 5190

South Asian (SAS) AF: 0.0342 AC: 165 AN: 4822

European-Finnish (FIN) AF: 0.0183 AC: 194 AN: 10598

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0681 AC: 4633 AN: 68016

Other (OTH) AF: 0.0634 AC: 134 AN: 2114

Alfa AF: 0.0626 Hom.: 46

Bravo AF: 0.0601

Asia WGS AF: 0.0390 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.80
PhyloP100		1.1
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: rs3758644; hg19: chr11-68366088;