rs188912013

Variant names:

• chr9-135484863-C-A
• rs188912013
• NM_014811.5:c.353C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-135484863-C-A
• chr9-135484863-C-G
• chr9-135484863-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014811.5(PPP1R26):​c.353C>A​(p.Pro118Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P118R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PPP1R26 NM_014811.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28
• Publications: 0 publications found

Genes affected

PPP1R26 (HGNC:29089): (protein phosphatase 1 regulatory subunit 26) Predicted to enable protein phosphatase inhibitor activity. Predicted to be involved in negative regulation of phosphatase activity. Predicted to be located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35052636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R26	NM_014811.5	c.353C>A	p.Pro118Gln	missense_variant	Exon 4 of 4	ENST00000356818.7	NP_055626.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R26	ENST00000356818.7	c.353C>A	p.Pro118Gln	missense_variant	Exon 4 of 4	1	NM_014811.5	ENSP00000349274.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455978 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 723892

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.00 AC: 0 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 85724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4204

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110390

Other (OTH) AF: 0.00 AC: 0 AN: 60062

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	0.0079	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.047	T;T;T;T;T
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.55	.;.;.;.;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.35	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.6	M;M;M;M;M
PhyloP100		4.3
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-6.3	.;.;D;.;.
REVEL	Benign	0.23
Sift	Uncertain	0.0030	.;.;D;.;.
Sift4G	Uncertain	0.015	D;D;D;D;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.30
MutPred		0.51		Gain of solvent accessibility (P = 0.0374);Gain of solvent accessibility (P = 0.0374);Gain of solvent accessibility (P = 0.0374);Gain of solvent accessibility (P = 0.0374);Gain of solvent accessibility (P = 0.0374);
MVP		0.27
MPC		0.35
ClinPred		0.92	D
GERP RS		5.2
PromoterAI		-0.0094	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.45
gMVP		0.17
Mutation Taster		=97/3	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: rs188912013; hg19: chr9-138376709;