NM_014811.5:c.341C>T

Variant names:

• chr9-135484851-C-T
• rs1787144475
• NM_014811.5:c.341C>T

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.341C>T​(p.Thr114Ile) 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. 15/22 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. T114A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPP1R26 NM_014811.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40
• 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=0.06424332).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014811.5. 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
	PPP1R26	NM_014811.5	MANE Select	c.341C>T	p.Thr114Ile	missense	Exon 4 of 4	NP_055626.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R26	ENST00000356818.7	TSL:1 MANE Select	c.341C>T	p.Thr114Ile	missense	Exon 4 of 4	ENSP00000349274.2	Q5T8A7
	PPP1R26	ENST00000401470.3	TSL:5	c.341C>T	p.Thr114Ile	missense	Exon 3 of 3	ENSP00000385826.3	Q5T8A7
	PPP1R26	ENST00000604351.5	TSL:3	c.341C>T	p.Thr114Ile	missense	Exon 3 of 3	ENSP00000473820.1	Q5T8A7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.18
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.053
Sift	Benign	0.030	D
Sift4G	Uncertain	0.044	D
Polyphen		0.020	B
Vest4		0.052
MutPred		0.22		Loss of glycosylation at T114 (P = 0.0312)
MVP		0.043
MPC		0.17
ClinPred		0.065	T
GERP RS		1.1
PromoterAI		0.0010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.077
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: rs1787144475; hg19: chr9-138376697;