NM_001166160.2:c.380T>C

Variant names:

• chr7-94910493-T-C
• NM_001166160.2:c.380T>C

Variant summary

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

The NM_001166160.2(PPP1R9A):​c.380T>C​(p.Phe127Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP1R9A NM_001166160.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.56
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.380T>C	p.Phe127Ser	missense	Exon 2 of 20	NP_001159632.1	Q9ULJ8-3
	PPP1R9A	NM_001166161.1		c.380T>C	p.Phe127Ser	missense	Exon 1 of 18	NP_001159633.1	Q9ULJ8-5
	PPP1R9A	NM_001166162.1		c.380T>C	p.Phe127Ser	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.380T>C	p.Phe127Ser	missense	Exon 2 of 20	ENSP00000405514.1	Q9ULJ8-3
	PPP1R9A	ENST00000289495.7	TSL:1	c.380T>C	p.Phe127Ser	missense	Exon 1 of 18	ENSP00000289495.7	Q9ULJ8-5
	PPP1R9A	ENST00000456331.6	TSL:1	c.380T>C	p.Phe127Ser	missense	Exon 1 of 17	ENSP00000402893.2	Q9ULJ8-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.32	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.011	D
Sift4G	Benign	0.97	T
Polyphen		1.0	D
Vest4		0.57
MutPred		0.24		Loss of stability (P = 0.0066)
MVP		0.92
MPC		0.93
ClinPred		0.98	D
GERP RS		5.7
PromoterAI		0.011	Neutral
Varity_R		0.48
gMVP		0.32
Mutation Taster		=79/21	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

hg19: chr7-94539805;