9-135484649-G-C

Variant names:

• chr9-135484649-G-C
• rs963098862
• NM_014811.5:c.139G>C

Variant summary

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

The NM_014811.5(PPP1R26):​c.139G>C​(p.Val47Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,194 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: PPP1R26 NM_014811.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.23
• 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R26	NM_014811.5	c.139G>C	p.Val47Leu	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.139G>C	p.Val47Leu	missense_variant	Exon 4 of 4	1	NM_014811.5	ENSP00000349274.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	0.0034	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;T;T;T
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.74	.;.;.;.;T
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.53	D;D;D;D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.7	M;M;M;M;M
PhyloP100		7.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.8	.;.;D;D;.
REVEL	Benign	0.22
Sift	Pathogenic	0.0	.;.;D;D;.
Sift4G	Uncertain	0.025	D;D;D;D;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.58
MutPred		0.23		Gain of catalytic residue at M49 (P = 0.0245);Gain of catalytic residue at M49 (P = 0.0245);Gain of catalytic residue at M49 (P = 0.0245);Gain of catalytic residue at M49 (P = 0.0245);Gain of catalytic residue at M49 (P = 0.0245);
MVP		0.27
MPC		0.16
ClinPred		0.96	D
GERP RS		5.4
PromoterAI		0.0052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.60
gMVP		0.74
Mutation Taster		=86/14	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: rs963098862; hg19: chr9-138376495;