7-95294079-T-C

Position:

• chr7-95294079-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.*3776T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,916 control chromosomes in the GnomAD database, including 25,302 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 0.55 (25295 hom., cov: 30)
  • Exomes 𝑓: 0.75 (7 hom.)
• Consequence: PPP1R9A NM_001166160.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R9A	NM_001166160.2	c.*3776T>C		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.*3776T>C		3_prime_UTR_variant	20/20	1	NM_001166160.2	ENSP00000405514.1
PPP1R9A	ENST00000456331.6	c.*3776T>C		3_prime_UTR_variant	17/17	1		ENSP00000402893.2
PPP1R9A	ENST00000340694.8	c.*3776T>C		3_prime_UTR_variant	16/16	5		ENSP00000344524.4
PPP1R9A	ENST00000433881.5	c.*3776T>C		3_prime_UTR_variant	16/16	5		ENSP00000398870.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83043 AN: 151770 Hom.: 25293 Cov.: 30

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.638

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.569

GnomAD4 exome AF: 0.750 AC: 21 AN: 28 Hom.: 7 Cov.: 0 AF XY: 0.722 AC XY: 13 AN XY: 18

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.750

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.722

GnomAD4 genome AF: 0.547 AC: 83055 AN: 151888 Hom.: 25295 Cov.: 30 AF XY: 0.545 AC XY: 40470 AN XY: 74202

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.563

Alfa AF: 0.651 Hom.: 35721

Bravo AF: 0.526

Asia WGS AF: 0.454 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.54

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: rs854544; hg19: chr7-94923391;