chr9-135484692-G-C

Variant names:

• chr9-135484692-G-C
• rs142346595
• NM_014811.5:c.182G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014811.5(PPP1R26):​c.182G>C​(p.Arg61Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,457,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. R61Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PPP1R26 NM_014811.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 3 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11679074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R26	NM_014811.5	c.182G>C	p.Arg61Pro	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.182G>C	p.Arg61Pro	missense_variant	Exon 4 of 4	1	NM_014811.5	ENSP00000349274.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000411 AC: 1 AN: 243050 AF XY: 0.00000754

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1457632 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 725128

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111400

Other (OTH) AF: 0.0000166 AC: 1 AN: 60318

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.011	T;T;T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.51	.;.;.;.;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N;N;N
PhyloP100		1.5
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.090	.;.;N;N;.
REVEL	Benign	0.23
Sift	Uncertain	0.016	.;.;D;D;.
Sift4G	Benign	0.33	T;T;T;T;T
Polyphen		0.12	B;B;B;B;B
Vest4		0.096
MutPred		0.32		Loss of MoRF binding (P = 0.0014);Loss of MoRF binding (P = 0.0014);Loss of MoRF binding (P = 0.0014);Loss of MoRF binding (P = 0.0014);Loss of MoRF binding (P = 0.0014);
MVP		0.31
MPC		0.23
ClinPred		0.052	T
GERP RS		-3.9
PromoterAI		0.00010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.12
gMVP		0.45
Mutation Taster		=82/18	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: rs142346595; hg19: chr9-138376538;