7-95296508-A-G

Variant names:

• chr7-95296508-A-G
• rs854548
• NM_001166160.2:c.*6205A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001166160.2(PPP1R9A):​c.*6205A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,478 control chromosomes in the GnomAD database, including 38,646 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 0.71 (38554 hom., cov: 33)
  • Exomes 𝑓: 0.67 (92 hom.)
• Consequence: PPP1R9A NM_001166160.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• Publications: 18 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R9A	NM_001166160.2	c.*6205A>G		downstream_gene_variant		ENST00000433360.6	NP_001159632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R9A	ENST00000433360.6	c.*6205A>G		downstream_gene_variant		1	NM_001166160.2	ENSP00000405514.1
PPP1R9A	ENST00000456331.6	c.*6205A>G		downstream_gene_variant		1		ENSP00000402893.2
PPP1R9A	ENST00000340694.8	c.*6205A>G		downstream_gene_variant		5		ENSP00000344524.4
PPP1R9A	ENST00000433881.5	c.*6205A>G		downstream_gene_variant		5		ENSP00000398870.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107687 AN: 151950 Hom.: 38543 Cov.: 33

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.745

GnomAD4 exome AF: 0.665 AC: 274 AN: 412 Hom.: 92 AF XY: 0.685 AC XY: 170 AN XY: 248

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.665 AC: 270 AN: 406

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.709 AC: 107743 AN: 152066 Hom.: 38554 Cov.: 33 AF XY: 0.708 AC XY: 52594 AN XY: 74314

African (AFR) AF: 0.630 AC: 26105 AN: 41444

American (AMR) AF: 0.726 AC: 11102 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2752 AN: 3472

East Asian (EAS) AF: 0.780 AC: 4024 AN: 5160

South Asian (SAS) AF: 0.800 AC: 3859 AN: 4822

European-Finnish (FIN) AF: 0.638 AC: 6737 AN: 10566

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50753 AN: 68000

Other (OTH) AF: 0.741 AC: 1563 AN: 2110

Alfa AF: 0.738 Hom.: 134522

Bravo AF: 0.709

Asia WGS AF: 0.758 AC: 2637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.77
PhyloP100		2.2
Mutation Taster		=97/3	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs854548; hg19: chr7-94925820; COSMIC: COSV55931628;