NM_001164161.2:c.228-3198C>G

Variant names:

• chr11-68541640-C-G
• rs7944870
• NM_001164161.2:c.228-3198C>G

Variant summary

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

The NM_001164161.2(PPP6R3):​c.228-3198C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,006 control chromosomes in the GnomAD database, including 4,666 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 0.24 (4666 hom., cov: 30)
• Consequence: PPP6R3 NM_001164161.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP6R3	NM_001164161.2	c.228-3198C>G		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.228-3198C>G		intron_variant	Intron 3 of 23	1	NM_001164161.2	ENSP00000377389.2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36571 AN: 151888 Hom.: 4664 Cov.: 30

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.241 AC: 36584 AN: 152006 Hom.: 4666 Cov.: 30 AF XY: 0.234 AC XY: 17349 AN XY: 74286

African (AFR) AF: 0.215 AC: 8925 AN: 41418

American (AMR) AF: 0.263 AC: 4021 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1171 AN: 5164

South Asian (SAS) AF: 0.167 AC: 806 AN: 4820

European-Finnish (FIN) AF: 0.170 AC: 1797 AN: 10562

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

European-Non Finnish (NFE) AF: 0.264 AC: 17936 AN: 67978

Other (OTH) AF: 0.273 AC: 576 AN: 2110

Alfa AF: 0.238 Hom.: 555

Bravo AF: 0.253

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	-0.92
CADD	Benign	1.7
DANN	Benign	0.59
PhyloP100		-0.21
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: rs7944870; hg19: chr11-68309108;