14-64550002-A-G

Variant names:

• chr14-64550002-A-G
• rs147817006
• NM_172365.3:c.5A>G

Variant summary

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

The NM_172365.3(PPP1R36):​c.5A>G​(p.Tyr2Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,569,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: PPP1R36 NM_172365.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.12
• Publications: 2 publications found

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]

PPP1R36 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0069179237).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172365.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R36	NM_172365.3	MANE Select	c.5A>G	p.Tyr2Cys	missense	Exon 1 of 12	NP_758953.1	Q96LQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R36	ENST00000298705.6	TSL:1 MANE Select	c.5A>G	p.Tyr2Cys	missense	Exon 1 of 12	ENSP00000298705.1	Q96LQ0
	PPP1R36	ENST00000927760.1		c.5A>G	p.Tyr2Cys	missense	Exon 1 of 11	ENSP00000597819.1
	PPP1R36	ENST00000884822.1		c.5A>G	p.Tyr2Cys	missense	Exon 1 of 11	ENSP00000554881.1

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152144 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000258 AC: 47 AN: 182268 AF XY: 0.000226

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00350

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000790

Gnomad OTH exome AF: 0.000414

GnomAD4 exome AF: 0.000119 AC: 168 AN: 1417500 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 76 AN XY: 701118

African (AFR) AF: 0.0000617 AC: 2 AN: 32412

American (AMR) AF: 0.000338 AC: 13 AN: 38474

Ashkenazi Jewish (ASJ) AF: 0.00383 AC: 97 AN: 25314

East Asian (EAS) AF: 0.00 AC: 0 AN: 37116

South Asian (SAS) AF: 0.00 AC: 0 AN: 80526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.0000285 AC: 31 AN: 1089300

Other (OTH) AF: 0.000427 AC: 25 AN: 58610

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152260 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74456

African (AFR) AF: 0.0000481 AC: 2 AN: 41554

American (AMR) AF: 0.000261 AC: 4 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000282 Hom.: 1

Bravo AF: 0.000204

ExAC AF: 0.000144 AC: 17

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.37
DANN	Benign	0.63
DEOGEN2	Benign	0.00098	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
PhyloP100		-2.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.040
Sift	Benign	0.17	T
Sift4G	Benign	0.18	T
Polyphen		0.79	P
Vest4		0.17
MVP		0.081
MPC		0.40
ClinPred		0.043	T
GERP RS		-6.4
PromoterAI		-0.17	Neutral
Varity_R		0.047
gMVP		0.16
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: rs147817006; hg19: chr14-65016720;