rs854543

Positions:

• chr7-95292231-C-A
• chr7-95292231-C-G
• chr7-95292231-C-T

Variant summary

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

The NM_001166160.2(PPP1R9A):​c.*1928C>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 0.804 in 152,426 control chromosomes in the GnomAD database, including 49,410 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 0.80 (49335 hom., cov: 33)
  • Exomes 𝑓: 0.73 (75 hom.)
• Consequence: PPP1R9A NM_001166160.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.756

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R9A	NM_001166160.2	c.*1928C>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.*1928C>A		3_prime_UTR_variant	20/20	1	NM_001166160.2	ENSP00000405514.1
PPP1R9A	ENST00000456331.6	c.*1928C>A		3_prime_UTR_variant	17/17	1		ENSP00000402893.2
PPP1R9A	ENST00000340694.8	c.*1928C>A		3_prime_UTR_variant	16/16	5		ENSP00000344524.4
PPP1R9A	ENST00000433881.5	c.*1928C>A		3_prime_UTR_variant	16/16	5		ENSP00000398870.1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122277 AN: 152022 Hom.: 49294 Cov.: 33

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.830

GnomAD4 exome AF: 0.734 AC: 210 AN: 286 Hom.: 75 Cov.: 0 AF XY: 0.722 AC XY: 130 AN XY: 180

Gnomad4 FIN exome AF: 0.730

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.804 AC: 122375 AN: 152140 Hom.: 49335 Cov.: 33 AF XY: 0.806 AC XY: 59949 AN XY: 74354

Gnomad4 AFR AF: 0.805

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.893

Gnomad4 SAS AF: 0.862

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.825

Alfa AF: 0.796 Hom.: 43934

Bravo AF: 0.815

Asia WGS AF: 0.842 AC: 2931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.33

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: rs854543; hg19: chr7-94921543;