rs12281742

Variant names:

• chr11-68536161-T-C
• rs12281742
• NM_001164161.2:c.-6-1498T>C

Variant summary

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

The NM_001164161.2(PPP6R3):​c.-6-1498T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,014 control chromosomes in the GnomAD database, including 8,729 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 0.32 (8729 hom., cov: 31)
• Consequence: PPP6R3 NM_001164161.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 8 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP6R3	NM_001164161.2	c.-6-1498T>C		intron_variant	Intron 2 of 23	ENST00000393800.7	NP_001157633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP6R3	ENST00000393800.7	c.-6-1498T>C		intron_variant	Intron 2 of 23	1	NM_001164161.2	ENSP00000377389.2

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48285 AN: 151894 Hom.: 8707 Cov.: 31

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.318 AC: 48352 AN: 152014 Hom.: 8729 Cov.: 31 AF XY: 0.308 AC XY: 22901 AN XY: 74300

African (AFR) AF: 0.485 AC: 20099 AN: 41408

American (AMR) AF: 0.288 AC: 4406 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3466

East Asian (EAS) AF: 0.227 AC: 1177 AN: 5176

South Asian (SAS) AF: 0.167 AC: 806 AN: 4818

European-Finnish (FIN) AF: 0.170 AC: 1799 AN: 10584

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18025 AN: 67958

Other (OTH) AF: 0.323 AC: 683 AN: 2114

Alfa AF: 0.295 Hom.: 1524

Bravo AF: 0.341

Asia WGS AF: 0.219 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.65
PhyloP100		-0.072
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: rs12281742; hg19: chr11-68303629;