rs854524

Variant names:

• chr7-95269499-G-A
• rs854524
• NM_001166160.2:c.3116G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-95269499-G-A
• chr7-95269499-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001166160.2(PPP1R9A):​c.3116G>A​(p.Arg1039Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 1,559,756 control chromosomes in the GnomAD database, including 239,659 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.59 (26943 hom., cov: 32)
  • Exomes 𝑓: 0.55 (212716 hom.)
• Consequence: PPP1R9A NM_001166160.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.72
• Publications: 33 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.3233136E-6).
• BP6: Variant 7-95269499-G-A is Benign according to our data. Variant chr7-95269499-G-A is described in ClinVar as Benign. ClinVar VariationId is 3058883.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

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.3116G>A	p.Arg1039Gln	missense	Exon 14 of 20	NP_001159632.1
	PPP1R9A	NM_001166161.1		c.2996G>A	p.Arg999Gln	missense	Exon 12 of 18	NP_001159633.1
	PPP1R9A	NM_001166162.1		c.3050G>A	p.Arg1017Gln	missense	Exon 12 of 17	NP_001159634.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R9A	ENST00000433360.6	TSL:1 MANE Select	c.3116G>A	p.Arg1039Gln	missense	Exon 14 of 20	ENSP00000405514.1
	PPP1R9A	ENST00000289495.7	TSL:1	c.2996G>A	p.Arg999Gln	missense	Exon 12 of 18	ENSP00000289495.7
	PPP1R9A	ENST00000456331.6	TSL:1	c.3050G>A	p.Arg1017Gln	missense	Exon 12 of 17	ENSP00000402893.2

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89842 AN: 151830 Hom.: 26919 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.625

GnomAD2 exomes AF: 0.574 AC: 133240 AN: 232092 AF XY: 0.566

Gnomad AFR exome AF: 0.679

Gnomad AMR exome AF: 0.635

Gnomad ASJ exome AF: 0.651

Gnomad EAS exome AF: 0.655

Gnomad FIN exome AF: 0.529

Gnomad NFE exome AF: 0.544

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.547 AC: 770745 AN: 1407808 Hom.: 212716 Cov.: 42 AF XY: 0.545 AC XY: 383289 AN XY: 702748

African (AFR) AF: 0.675 AC: 21704 AN: 32172

American (AMR) AF: 0.632 AC: 27535 AN: 43574

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 16708 AN: 25864

East Asian (EAS) AF: 0.688 AC: 27119 AN: 39398

South Asian (SAS) AF: 0.503 AC: 42414 AN: 84384

European-Finnish (FIN) AF: 0.538 AC: 21038 AN: 39086

Middle Eastern (MID) AF: 0.602 AC: 3410 AN: 5662

European-Non Finnish (NFE) AF: 0.536 AC: 577691 AN: 1078714

Other (OTH) AF: 0.562 AC: 33126 AN: 58954

GnomAD4 genome AF: 0.592 AC: 89914 AN: 151948 Hom.: 26943 Cov.: 32 AF XY: 0.590 AC XY: 43800 AN XY: 74250

African (AFR) AF: 0.680 AC: 28209 AN: 41454

American (AMR) AF: 0.615 AC: 9377 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2278 AN: 3468

East Asian (EAS) AF: 0.641 AC: 3315 AN: 5168

South Asian (SAS) AF: 0.502 AC: 2423 AN: 4822

European-Finnish (FIN) AF: 0.525 AC: 5532 AN: 10540

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36632 AN: 67948

Other (OTH) AF: 0.627 AC: 1320 AN: 2104

Alfa AF: 0.566 Hom.: 72529

Bravo AF: 0.607

TwinsUK AF: 0.536 AC: 1986

ALSPAC AF: 0.547 AC: 2107

ESP6500AA AF: 0.679 AC: 2128

ESP6500EA AF: 0.557 AC: 3991

ExAC AF: 0.572 AC: 67625

Asia WGS AF: 0.595 AC: 2074 AN: 3478

EpiCase AF: 0.552

EpiControl AF: 0.555

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PPP1R9A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Benign	0.41
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0000073	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.7
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.81	N
REVEL	Benign	0.026
Sift	Benign	1.0	T
Sift4G	Benign	0.59	T
Vest4		0.045
MPC		0.19
ClinPred		0.0049	T
GERP RS		2.5
gMVP		0.12
Mutation Taster		=98/2	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: rs854524; hg19: chr7-94898811; COSMIC: COSV56912578;