chr9-135484682-G-A

Variant names:

• chr9-135484682-G-A
• rs201579051
• NM_014811.5:c.172G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014811.5(PPP1R26):​c.172G>A​(p.Gly58Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,609,970 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: PPP1R26 NM_014811.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.158
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02818811).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R26	NM_014811.5	c.172G>A	p.Gly58Arg	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.172G>A	p.Gly58Arg	missense_variant	Exon 4 of 4	1	NM_014811.5	ENSP00000349274.2

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0000654

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000452 AC: 11 AN: 243398 AF XY: 0.0000376

Gnomad AFR exome AF: 0.000132

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000549

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000104 AC: 152 AN: 1457734 Hom.: 0 Cov.: 30 AF XY: 0.000102 AC XY: 74 AN XY: 725216

African (AFR) AF: 0.0000598 AC: 2 AN: 33464

American (AMR) AF: 0.0000224 AC: 1 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

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

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86184

European-Finnish (FIN) AF: 0.0000200 AC: 1 AN: 50120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.000128 AC: 142 AN: 1111540

Other (OTH) AF: 0.0000663 AC: 4 AN: 60332

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74378

African (AFR) AF: 0.0000965 AC: 4 AN: 41464

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68042

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

Alfa AF: 0.0000284 Hom.: 0

Bravo AF: 0.0000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000662 AC: 8

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 24, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.172G>A (p.G58R) alteration is located in exon 4 (coding exon 1) of the PPP1R26 gene. This alteration results from a G to A substitution at nucleotide position 172, causing the glycine (G) at amino acid position 58 to be replaced by an arginine (R). 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	0.086
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.89
DANN	Benign	0.87
DEOGEN2	Benign	0.0045	T;T;T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.40	.;.;.;.;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.028	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;L;L;L
PhyloP100		0.16
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.010	.;.;N;N;.
REVEL	Benign	0.057
Sift	Benign	0.35	.;.;T;T;.
Sift4G	Benign	0.081	T;T;T;T;T
Polyphen		0.025	B;B;B;B;B
Vest4		0.068
MutPred		0.17		Gain of MoRF binding (P = 0.043);Gain of MoRF binding (P = 0.043);Gain of MoRF binding (P = 0.043);Gain of MoRF binding (P = 0.043);Gain of MoRF binding (P = 0.043);
MVP		0.11
MPC		0.35
ClinPred		0.0095	T
GERP RS		0.030
PromoterAI		0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.037
gMVP		0.11
Mutation Taster		=100/0	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: rs201579051; hg19: chr9-138376528; COSMIC: COSV63357135; COSMIC: COSV63357135;