NM_001166160.2:c.3116G>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001166160.2(PPP1R9A):​c.3116G>C​(p.Arg1039Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000163 in 1,408,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1039Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: PPP1R9A NM_001166160.2 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0716002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R9A	NM_001166160.2	c.3116G>C	p.Arg1039Pro	missense_variant	Exon 14 of 20	ENST00000433360.6	NP_001159632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R9A	ENST00000433360.6	c.3116G>C	p.Arg1039Pro	missense_variant	Exon 14 of 20	1	NM_001166160.2	ENSP00000405514.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000163 AC: 23 AN: 1408888 Hom.: 0 Cov.: 42 AF XY: 0.0000171 AC XY: 12 AN XY: 703218

African (AFR) AF: 0.00 AC: 0 AN: 32204

American (AMR) AF: 0.00 AC: 0 AN: 43634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25870

East Asian (EAS) AF: 0.00 AC: 0 AN: 39428

South Asian (SAS) AF: 0.00 AC: 0 AN: 84464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.0000204 AC: 22 AN: 1079550

Other (OTH) AF: 0.0000170 AC: 1 AN: 58990

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	21
DANN	Benign	0.96
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.65	T;.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.072	T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		1.7
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.65	N;N;N;N
REVEL	Benign	0.030
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Benign	0.23	T;T;T;T
Vest4		0.13
MVP		0.15
MPC		0.24
ClinPred		0.17	T
GERP RS		2.5
gMVP		0.21
Mutation Taster		=80/20	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: rs854524; hg19: chr7-94898811;