7-94911005-C-G

Variant names:

• chr7-94911005-C-G
• rs765340205
• NM_001166160.2:c.892C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001166160.2(PPP1R9A):​c.892C>G​(p.Gln298Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000090 (0 hom.)
• Consequence: PPP1R9A NM_001166160.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09716058).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166160.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R9A	NM_001166160.2	MANE Select	c.892C>G	p.Gln298Glu	missense	Exon 2 of 20	NP_001159632.1	Q9ULJ8-3
	PPP1R9A	NM_001166161.1		c.892C>G	p.Gln298Glu	missense	Exon 1 of 18	NP_001159633.1	Q9ULJ8-5
	PPP1R9A	NM_001166162.1		c.892C>G	p.Gln298Glu	missense	Exon 1 of 17	NP_001159634.1	Q9ULJ8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R9A	ENST00000433360.6	TSL:1 MANE Select	c.892C>G	p.Gln298Glu	missense	Exon 2 of 20	ENSP00000405514.1	Q9ULJ8-3
	PPP1R9A	ENST00000289495.7	TSL:1	c.892C>G	p.Gln298Glu	missense	Exon 1 of 18	ENSP00000289495.7	Q9ULJ8-5
	PPP1R9A	ENST00000456331.6	TSL:1	c.892C>G	p.Gln298Glu	missense	Exon 1 of 17	ENSP00000402893.2	Q9ULJ8-4

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152100 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251304 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000903 AC: 132 AN: 1461862 Hom.: 0 Cov.: 32 AF XY: 0.0000894 AC XY: 65 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000119 AC: 132 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152100 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74290

African (AFR) AF: 0.0000242 AC: 1 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.67
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.1
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.25
Sift	Benign	0.10	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.052
MutPred		0.089		Loss of methylation at K301 (P = 0.0891)
MVP		0.56
MPC		0.18
ClinPred		0.077	T
GERP RS		4.8
Varity_R		0.12
gMVP		0.11
Mutation Taster		=93/7	polymorphism

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: rs765340205; hg19: chr7-94540317;