rs854534

Variant names:

• chr7-95280183-G-A
• rs854534
• NM_001166160.2:c.3297-3835G>A

Variant summary

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

The NM_001166160.2(PPP1R9A):​c.3297-3835G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,052 control chromosomes in the GnomAD database, including 11,111 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 (11111 hom., cov: 32)
• Consequence: PPP1R9A NM_001166160.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R9A	NM_001166160.2	c.3297-3835G>A		intron_variant	Intron 16 of 19	ENST00000433360.6	NP_001159632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R9A	ENST00000433360.6	c.3297-3835G>A		intron_variant	Intron 16 of 19	1	NM_001166160.2	ENSP00000405514.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56868 AN: 151934 Hom.: 11113 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.374 AC: 56886 AN: 152052 Hom.: 11111 Cov.: 32 AF XY: 0.371 AC XY: 27551 AN XY: 74324

African (AFR) AF: 0.290 AC: 12041 AN: 41478

American (AMR) AF: 0.388 AC: 5928 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1989 AN: 3464

East Asian (EAS) AF: 0.450 AC: 2324 AN: 5170

South Asian (SAS) AF: 0.318 AC: 1534 AN: 4822

European-Finnish (FIN) AF: 0.304 AC: 3214 AN: 10582

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28460 AN: 67958

Other (OTH) AF: 0.439 AC: 928 AN: 2112

Alfa AF: 0.413 Hom.: 44837

Bravo AF: 0.380

Asia WGS AF: 0.372 AC: 1296 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.56
DANN	Benign	0.58
PhyloP100		-1.3
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: rs854534; hg19: chr7-94909495;