7-95268921-T-C

Variant names:

• chr7-95268921-T-C
• rs854523
• NM_001166160.2:c.2823+214T>C

Variant summary

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

The NM_001166160.2(PPP1R9A):​c.2823+214T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,030 control chromosomes in the GnomAD database, including 19,298 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 0.50 (19298 hom., cov: 32)
• Consequence: PPP1R9A NM_001166160.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.674
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R9A	NM_001166160.2	c.2823+214T>C		intron_variant	Intron 13 of 19	ENST00000433360.6	NP_001159632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R9A	ENST00000433360.6	c.2823+214T>C		intron_variant	Intron 13 of 19	1	NM_001166160.2	ENSP00000405514.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75958 AN: 151910 Hom.: 19294 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.500 AC: 75997 AN: 152030 Hom.: 19298 Cov.: 32 AF XY: 0.500 AC XY: 37176 AN XY: 74304

African (AFR) AF: 0.413 AC: 17141 AN: 41464

American (AMR) AF: 0.541 AC: 8265 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2271 AN: 3466

East Asian (EAS) AF: 0.550 AC: 2826 AN: 5142

South Asian (SAS) AF: 0.445 AC: 2147 AN: 4828

European-Finnish (FIN) AF: 0.519 AC: 5485 AN: 10570

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.528 AC: 35881 AN: 67982

Other (OTH) AF: 0.551 AC: 1162 AN: 2108

Alfa AF: 0.533 Hom.: 26958

Bravo AF: 0.504

Asia WGS AF: 0.479 AC: 1670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		-0.67
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: rs854523; hg19: chr7-94898233;