9-135484775-G-C

Variant names:

• chr9-135484775-G-C
• rs142421416
• NM_014811.5:c.265G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014811.5(PPP1R26):​c.265G>C​(p.Val89Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V89M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPP1R26 NM_014811.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.433
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052094996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R26	NM_014811.5	c.265G>C	p.Val89Leu	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.265G>C	p.Val89Leu	missense_variant	Exon 4 of 4	1	NM_014811.5	ENSP00000349274.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 15, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.265G>C (p.V89L) alteration is located in exon 4 (coding exon 1) of the PPP1R26 gene. This alteration results from a G to C substitution at nucleotide position 265, causing the valine (V) at amino acid position 89 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.021
DANN	Benign	0.54
DEOGEN2	Benign	0.0013	T;T;T;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.31	.;.;.;.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.052	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N;N;N;N;N
PhyloP100		-0.43
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.67	.;.;N;N;.
REVEL	Benign	0.023
Sift	Benign	0.27	.;.;T;T;.
Sift4G	Benign	0.79	T;T;T;T;T
Polyphen		0.013	B;B;B;B;B
Vest4		0.017
MutPred		0.17		Loss of glycosylation at T88 (P = 0.0907);Loss of glycosylation at T88 (P = 0.0907);Loss of glycosylation at T88 (P = 0.0907);Loss of glycosylation at T88 (P = 0.0907);Loss of glycosylation at T88 (P = 0.0907);
MVP		0.32
MPC		0.16
ClinPred		0.057	T
GERP RS		-1.6
PromoterAI		0.011	Neutral
Varity_R		0.023
gMVP		0.045
Mutation Taster		=96/4	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: rs142421416; hg19: chr9-138376621;