rs500079

Positions:

• chr19-48875737-A-C
• chr19-48875737-A-G
• chr19-48875737-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014330.5(PPP1R15A):​c.1789A>C​(p.Thr597Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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. T597A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PPP1R15A NM_014330.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

Genes affected

PPP1R15A (HGNC:14375): (protein phosphatase 1 regulatory subunit 15A) This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The induction of this gene by ionizing radiation occurs in certain cell lines regardless of p53 status, and its protein response is correlated with apoptosis following ionizing radiation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07949975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R15A	NM_014330.5	c.1789A>C	p.Thr597Pro	missense_variant	3/3	ENST00000200453.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R15A	ENST00000200453.6	c.1789A>C	p.Thr597Pro	missense_variant	3/3	1	NM_014330.5	P2
PPP1R15A	ENST00000704027.1	c.1837A>C	p.Thr613Pro	missense_variant	2/2			A2
PPP1R15A	ENST00000704026.1	c.1504A>C	p.Thr502Pro	missense_variant	4/4			A2
PPP1R15A	ENST00000600406.2	c.*644A>C		3_prime_UTR_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.063	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.033
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.011	D
Polyphen		0.023	B
Vest4		0.14
MutPred		0.23		Loss of phosphorylation at T597 (P = 0.0304);
MVP		0.12
MPC		0.11
ClinPred		0.25	T
GERP RS		2.8
Varity_R		0.48
gMVP		0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs500079; hg19: chr19-49378994;