rs854522

Positions:

• chr7-95268489-T-C

Variant summary

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

The NM_001166160.2(PPP1R9A):​c.2666-61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,573,008 control chromosomes in the GnomAD database, including 138,331 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 0.37 (10979 hom., cov: 31)
  • Exomes 𝑓: 0.42 (127352 hom.)
• Consequence: PPP1R9A NM_001166160.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191

Genes affected

PPP1R9A (HGNC:14946): (protein phosphatase 1 regulatory subunit 9A) This gene is imprinted, and located in a cluster of imprinted genes on chromosome 7q12. This gene is transcribed in both neuronal and multiple embryonic tissues, and it is maternally expressed mainly in embryonic skeletal muscle tissues and biallelically expressed in other embryonic tissues. The protein encoded by this gene includes a PDZ domain and a sterile alpha motif (SAM). It is a regulatory subunit of protein phosphatase I, and controls actin cytoskeleton reorganization. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R9A	NM_001166160.2	c.2666-61T>C		intron_variant		ENST00000433360.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R9A	ENST00000433360.6	c.2666-61T>C		intron_variant		1	NM_001166160.2

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55897 AN: 151846 Hom.: 10980 Cov.: 31

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.423

GnomAD4 exome AF: 0.420 AC: 597103 AN: 1421046 Hom.: 127352 AF XY: 0.419 AC XY: 295567 AN XY: 706250

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.336

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.447

Gnomad4 SAS exome AF: 0.326

Gnomad4 FIN exome AF: 0.382

Gnomad4 NFE exome AF: 0.435

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.368 AC: 55906 AN: 151962 Hom.: 10979 Cov.: 31 AF XY: 0.365 AC XY: 27133 AN XY: 74276

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.422

Alfa AF: 0.425 Hom.: 12314

Bravo AF: 0.366

Asia WGS AF: 0.340 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs854522; hg19: chr7-94897801; COSMIC: COSV56888179;