chr20-38900588-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_015568.4(PPP1R16B):​c.475G>A​(p.Asp159Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 1,449,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

PPP1R16B
NM_015568.4 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.15
Variant links:
Genes affected
PPP1R16B (HGNC:15850): (protein phosphatase 1 regulatory subunit 16B) The protein encoded by this gene is membrane-associated and contains five ankyrin repeats, a protein phosphatase-1-interacting domain, and a carboxy-terminal CAAX box domain. Synthesis of the encoded protein is inhibited by transforming growth factor beta-1. The protein may bind to the membrane through its CAAX box domain and may act as a signaling molecule through interaction with protein phosphatase-1. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.76
BS2
High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPP1R16BNM_015568.4 linkuse as main transcriptc.475G>A p.Asp159Asn missense_variant 5/11 ENST00000299824.6
PPP1R16BNM_001172735.3 linkuse as main transcriptc.475G>A p.Asp159Asn missense_variant 5/10
PPP1R16BXM_011528768.4 linkuse as main transcriptc.487G>A p.Asp163Asn missense_variant 4/10
PPP1R16BXM_047440086.1 linkuse as main transcriptc.-26-2080G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPP1R16BENST00000299824.6 linkuse as main transcriptc.475G>A p.Asp159Asn missense_variant 5/111 NM_015568.4 P1Q96T49-1
PPP1R16BENST00000373331.2 linkuse as main transcriptc.475G>A p.Asp159Asn missense_variant 5/105 Q96T49-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.0000159
AC:
23
AN:
1449686
Hom.:
0
Cov.:
30
AF XY:
0.0000180
AC XY:
13
AN XY:
720648
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000259
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.0000190
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

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 02, 2022The c.475G>A (p.D159N) alteration is located in exon 5 (coding exon 4) of the PPP1R16B gene. This alteration results from a G to A substitution at nucleotide position 475, causing the aspartic acid (D) at amino acid position 159 to be replaced by an asparagine (N). 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
0.15
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;.
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Benign
0.012
T
MetaRNN
Pathogenic
0.76
D;D
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.0
L;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
0.36
N;N
REVEL
Benign
0.23
Sift
Benign
0.60
T;T
Sift4G
Benign
0.83
T;T
Polyphen
0.97
D;.
Vest4
0.76
MutPred
0.60
Loss of catalytic residue at D159 (P = 0.188);Loss of catalytic residue at D159 (P = 0.188);
MVP
0.70
MPC
2.4
ClinPred
0.77
D
GERP RS
5.0
Varity_R
0.15
gMVP
0.67

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: rs866362326; hg19: chr20-37529231; COSMIC: COSV100239202; COSMIC: COSV100239202; API