rs375238310

Variant names:

• chr9-135484646-C-G
• rs375238310
• NM_014811.5:c.136C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-135484646-C-G
• chr9-135484646-C-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.136C>G​(p.Arg46Gly) 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. R46W) 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: 0.619
• 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=0.043804437).

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.136C>G	p.Arg46Gly	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.136C>G	p.Arg46Gly	missense	Exon 4 of 4	ENSP00000349274.2	Q5T8A7
	PPP1R26	ENST00000401470.3	TSL:5	c.136C>G	p.Arg46Gly	missense	Exon 3 of 3	ENSP00000385826.3	Q5T8A7
	PPP1R26	ENST00000604351.5	TSL:3	c.136C>G	p.Arg46Gly	missense	Exon 3 of 3	ENSP00000473820.1	Q5T8A7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.099
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.093
DANN	Benign	0.92
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.62
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.22
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.022	D
Polyphen		0.011	B
Vest4		0.17
MutPred		0.39		Loss of MoRF binding (P = 0.019)
MVP		0.40
MPC		0.21
ClinPred		0.17	T
GERP RS		-11
PromoterAI		-0.0060	Neutral
Varity_R		0.16
gMVP		0.26
Mutation Taster		=88/12	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: rs375238310; hg19: chr9-138376492;