14-64568371-C-T

Variant names:

• chr14-64568371-C-T
• rs1596735308
• NM_172365.3:c.457C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_172365.3(PPP1R36):​c.457C>T​(p.Leu153Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000726 in 1,378,092 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PPP1R36 NM_172365.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.97

Genes affected

PPP1R36 (HGNC:20097): (protein phosphatase 1 regulatory subunit 36) Predicted to enable phosphatase binding activity and protein phosphatase inhibitor activity. Predicted to be involved in negative regulation of phosphatase activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259076 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 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
PPP1R36	NM_172365.3	c.457C>T	p.Leu153Phe	missense_variant	Exon 7 of 12	ENST00000298705.6	NP_758953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R36	ENST00000298705.6	c.457C>T	p.Leu153Phe	missense_variant	Exon 7 of 12	1	NM_172365.3	ENSP00000298705.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1378092 Hom.: 0 Cov.: 23 AF XY: 0.00000145 AC XY: 1 AN XY: 688242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.44e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.457C>T (p.L153F) alteration is located in exon 7 (coding exon 7) of the PPP1R36 gene. This alteration results from a C to T substitution at nucleotide position 457, causing the leucine (L) at amino acid position 153 to be replaced by a phenylalanine (F). 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	Uncertain	0.49
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.090	T;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.78
MutPred		0.35		Gain of catalytic residue at M154 (P = 0.0061);.;
MVP		0.73
MPC		0.64
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.61
gMVP		0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs1596735308; hg19: chr14-65035089;