chr6-30069239-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_021959.3(PPP1R11):​c.314C>T​(p.Pro105Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,612,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

PPP1R11
NM_021959.3 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.469
Variant links:
Genes affected
PPP1R11 (HGNC:9285): (protein phosphatase 1 regulatory inhibitor subunit 11) This gene encodes a specific inhibitor of protein phosphatase-1 (PP1) with a differential sensitivity toward the metal-independent and metal-dependent forms of PP1. The gene is located within the major histocompatibility complex class I region on chromosome 6. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.055764556).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPP1R11NM_021959.3 linkuse as main transcriptc.314C>T p.Pro105Leu missense_variant 3/3 ENST00000376772.8
PPP1R11XM_047419279.1 linkuse as main transcriptc.314C>T p.Pro105Leu missense_variant 4/4
PPP1R11XM_047419280.1 linkuse as main transcriptc.314C>T p.Pro105Leu missense_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPP1R11ENST00000376772.8 linkuse as main transcriptc.314C>T p.Pro105Leu missense_variant 3/31 NM_021959.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152096
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000122
AC:
3
AN:
245686
Hom.:
0
AF XY:
0.00000747
AC XY:
1
AN XY:
133824
show subpopulations
Gnomad AFR exome
AF:
0.000132
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000151
AC:
22
AN:
1460452
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
726552
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.0000448
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152214
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.00000851
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 21, 2024The c.314C>T (p.P105L) alteration is located in exon 3 (coding exon 3) of the PPP1R11 gene. This alteration results from a C to T substitution at nucleotide position 314, causing the proline (P) at amino acid position 105 to be replaced by a leucine (L). 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
0.084
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
18
DANN
Benign
0.95
DEOGEN2
Benign
0.024
T;T;T;T;T;T
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.031
N
M_CAP
Benign
0.0028
T
MetaRNN
Benign
0.056
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
.;L;.;.;.;.
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.4
N;N;N;N;N;N
REVEL
Benign
0.027
Sift
Uncertain
0.023
D;D;D;D;D;D
Sift4G
Uncertain
0.040
D;T;D;D;D;D
Polyphen
0.0
.;B;.;.;.;.
Vest4
0.13
MutPred
0.25
.;Loss of glycosylation at P105 (P = 0.0211);.;.;.;.;
MVP
0.043
MPC
0.98
ClinPred
0.038
T
GERP RS
2.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.040
gMVP
0.22

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs775916081; hg19: chr6-30037016; API