rs854547

Positions:

• chr7-95294544-G-A
• chr7-95294544-G-C
• chr7-95294544-G-T

Variant summary

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

The NM_001166160.2(PPP1R9A):​c.*4241G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,978 control chromosomes in the GnomAD database, including 23,119 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 0.54 (23115 hom., cov: 31)
  • Exomes 𝑓: 0.90 (4 hom.)
• Consequence: PPP1R9A NM_001166160.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R9A	NM_001166160.2	c.*4241G>A		3_prime_UTR_variant	20/20	ENST00000433360.6	NP_001159632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R9A	ENST00000433360.6	c.*4241G>A		3_prime_UTR_variant	20/20	1	NM_001166160.2	ENSP00000405514
PPP1R9A	ENST00000456331.6	c.*4241G>A		3_prime_UTR_variant	17/17	1		ENSP00000402893
PPP1R9A	ENST00000340694.8	c.*4241G>A		3_prime_UTR_variant	16/16	5		ENSP00000344524	A1
PPP1R9A	ENST00000433881.5	c.*4241G>A		3_prime_UTR_variant	16/16	5		ENSP00000398870	A1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81978 AN: 151850 Hom.: 23116 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.573

GnomAD4 exome AF: 0.900 AC: 9 AN: 10 Hom.: 4 Cov.: 0 AF XY: 1.00 AC XY: 8 AN XY: 8

Gnomad4 ASJ exome AF: 1.00

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.540 AC: 81988 AN: 151968 Hom.: 23115 Cov.: 31 AF XY: 0.538 AC XY: 39981 AN XY: 74256

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.567

Alfa AF: 0.615 Hom.: 48782

Bravo AF: 0.528

Asia WGS AF: 0.449 AC: 1564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs854547; hg19: chr7-94923856;