11-68495902-T-C

Variant names:

• chr11-68495902-T-C
• rs12272917
• NM_001164161.2:c.-157-23599T>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.-157-23599T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,192 control chromosomes in the GnomAD database, including 4,299 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 (4299 hom., cov: 32)
• Consequence: PPP6R3 NM_001164161.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.990
• Publications: 19 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=-0.89).
• 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.-157-23599T>C		intron_variant	Intron 1 of 23	ENST00000393800.7	NP_001157633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP6R3	ENST00000393800.7	c.-157-23599T>C		intron_variant	Intron 1 of 23	1	NM_001164161.2	ENSP00000377389.2

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35080 AN: 152074 Hom.: 4297 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.320

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: 0.231 AC: 35092 AN: 152192 Hom.: 4299 Cov.: 32 AF XY: 0.224 AC XY: 16705 AN XY: 74418

African (AFR) AF: 0.204 AC: 8483 AN: 41522

American (AMR) AF: 0.253 AC: 3859 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 751 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1169 AN: 5186

South Asian (SAS) AF: 0.166 AC: 801 AN: 4830

European-Finnish (FIN) AF: 0.165 AC: 1754 AN: 10606

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17153 AN: 67986

Other (OTH) AF: 0.266 AC: 561 AN: 2112

Alfa AF: 0.226 Hom.: 5457

Bravo AF: 0.243

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.73
PhyloP100		0.99
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: rs12272917; hg19: chr11-68263370;