9-135484775-G-A

Variant names:

• chr9-135484775-G-A
• rs142421416
• NM_014811.5:c.265G>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.265G>A​(p.Val89Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000278 in 1,611,190 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V89L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: PPP1R26 NM_014811.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.433
• 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=0.0111320615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R26	NM_014811.5	c.265G>A	p.Val89Met	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>A	p.Val89Met	missense_variant	Exon 4 of 4	1	NM_014811.5	ENSP00000349274.2

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152260 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000274 AC: 67 AN: 244326 AF XY: 0.000323

Gnomad AFR exome AF: 0.000198

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.0000549

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000280 AC: 408 AN: 1458930 Hom.: 0 Cov.: 30 AF XY: 0.000291 AC XY: 211 AN XY: 725694

African (AFR) AF: 0.0000897 AC: 3 AN: 33428

American (AMR) AF: 0.000134 AC: 6 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26120

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39674

South Asian (SAS) AF: 0.000998 AC: 86 AN: 86130

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 51950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5104

European-Non Finnish (NFE) AF: 0.000264 AC: 293 AN: 1111572

Other (OTH) AF: 0.000232 AC: 14 AN: 60268

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152260 Hom.: 0 Cov.: 33 AF XY: 0.000296 AC XY: 22 AN XY: 74396

African (AFR) AF: 0.000121 AC: 5 AN: 41474

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: 5198

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68038

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

Alfa AF: 0.000469 Hom.: 0

Bravo AF: 0.000212

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000223 AC: 27

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.265G>A (p.V89M) 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 265, causing the valine (V) at amino acid position 89 to be replaced by a methionine (M). 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	0.085
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.25
DANN	Benign	0.89
DEOGEN2	Benign	0.0033	T;T;T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.38	.;.;.;.;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.011	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N;N;N;N;N
PhyloP100		-0.43
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.88	.;.;N;N;.
REVEL	Benign	0.042
Sift	Benign	0.037	.;.;D;D;.
Sift4G	Benign	0.10	T;T;T;T;T
Polyphen		0.062	B;B;B;B;B
Vest4		0.034
MVP		0.35
MPC		0.16
ClinPred		0.0024	T
GERP RS		-1.6
PromoterAI		0.0025	Neutral
Varity_R		0.022
gMVP		0.052
Mutation Taster		=99/1	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; COSMIC: COSV63355036; COSMIC: COSV63355036;