rs371967332

Variant names:

• chr9-135484527-C-A
• rs371967332
• NM_014811.5:c.17C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-135484527-C-A
• chr9-135484527-C-T

Variant summary

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

The NM_014811.5(PPP1R26):​c.17C>A​(p.Ala6Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,456 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A6T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PPP1R26 NM_014811.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R26	NM_014811.5	c.17C>A	p.Ala6Asp	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.17C>A	p.Ala6Asp	missense_variant	Exon 4 of 4	1	NM_014811.5	ENSP00000349274.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450456 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 722038

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32576

American (AMR) AF: 0.00 AC: 0 AN: 41374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25514

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4342

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109326

Other (OTH) AF: 0.00 AC: 0 AN: 59692

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.044843), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T;T;T;T;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.67	.;.;.;.;T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.63	D;D;D;D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.6	M;M;M;M;M
PhyloP100		2.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.2	.;.;D;D;.
REVEL	Benign	0.23
Sift	Uncertain	0.0020	.;.;D;D;.
Sift4G	Uncertain	0.0030	D;D;D;D;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.60
MutPred		0.36		Gain of disorder (P = 0.0725);Gain of disorder (P = 0.0725);Gain of disorder (P = 0.0725);Gain of disorder (P = 0.0725);Gain of disorder (P = 0.0725);
MVP		0.15
MPC		0.39
ClinPred		0.98	D
GERP RS		5.4
PromoterAI		-0.025	Neutral
Varity_R		0.84
gMVP		0.68
Mutation Taster		=83/17	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: rs371967332; hg19: chr9-138376373;