Variant 20-38918572-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015568.4(PPP1R16B):c.1610A>G(p.Tyr537Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,393,546 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: 0.0000014 ( 0 hom. )

Consequence

PPP1R16B
NM_015568.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09

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]

PPP1R16B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.745

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PPP1R16B	NM_015568.4 linkuse as main transcript	c.1610A>G	p.Tyr537Cys	missense_variant	11/11	ENST00000299824.6	NP_056383.1
PPP1R16B	NM_001172735.3 linkuse as main transcript	c.1484A>G	p.Tyr495Cys	missense_variant	10/10		NP_001166206.1
PPP1R16B	XM_011528768.4 linkuse as main transcript	c.1622A>G	p.Tyr541Cys	missense_variant	10/10		XP_011527070.1
PPP1R16B	XM_047440086.1 linkuse as main transcript	c.1013A>G	p.Tyr338Cys	missense_variant	7/7		XP_047296042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R16B	ENST00000299824.6 linkuse as main transcript	c.1610A>G	p.Tyr537Cys	missense_variant	11/11	1	NM_015568.4	ENSP00000299824	P1	Q96T49-1
PPP1R16B	ENST00000373331.2 linkuse as main transcript	c.1484A>G	p.Tyr495Cys	missense_variant	10/10	5		ENSP00000362428		Q96T49-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1393546

Hom.:

Cov.:

AF XY:

0.00000292

AC XY:

AN XY:

685396

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000349

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Sep 23, 2023

The c.1610A>G (p.Y537C) alteration is located in exon 11 (coding exon 10) of the PPP1R16B gene. This alteration results from a A to G substitution at nucleotide position 1610, causing the tyrosine (Y) at amino acid position 537 to be replaced by a cysteine (C). 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

0.33

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.75

D;D

MetaSVM

Uncertain

0.24

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.60

Sift

Uncertain

0.0070

D;T

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.76

MutPred

0.36

Loss of phosphorylation at Y537 (P = 0.0282);.;

MVP

0.73

MPC

1.5

ClinPred

0.97

GERP RS

5.3

Varity_R

0.29

gMVP

0.56

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over