Genetic Variant PPP1R14B:p.Gly9Ala (chr11-64246648-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138689.3(PPP1R14B):c.26G>C(p.Gly9Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000916 in 1,091,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G9D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)

Exomes 𝑓: 9.2e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PPP1R14B
NM_138689.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

0 publications found

Variant links:

Genes affected

PPP1R14B (HGNC:9057): (protein phosphatase 1 regulatory inhibitor subunit 14B) Predicted to enable protein serine/threonine phosphatase inhibitor activity. Predicted to be involved in innate immune response. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PPP1R14B links:

PPP1R14B-AS1 (HGNC:54233): (PPP1R14B antisense RNA 1)

PPP1R14B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06763241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R14B	NM_138689.3 link	c.26G>C	p.Gly9Ala	missense_variant	Exon 1 of 4	ENST00000309318.8	NP_619634.1	Q96C90
PPP1R14B-AS1	NR_135087.1 link	n.224+559C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R14B	ENST00000309318.8 link	c.26G>C	p.Gly9Ala	missense_variant	Exon 1 of 4	1	NM_138689.3	ENSP00000310117.3		Q96C90

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149374

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.16e-7

AC:

AN:

1091952

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

520300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22320

American (AMR)

AF:

0.000123

AC:

AN:

8146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13650

East Asian (EAS)

AF:

0.00

AC:

AN:

25700

South Asian (SAS)

AF:

0.00

AC:

AN:

23542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2898

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

920354

Other (OTH)

AF:

0.00

AC:

AN:

42902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

149374

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72842

African (AFR)

AF:

0.00

AC:

AN:

41086

American (AMR)

AF:

0.00

AC:

AN:

14994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67112

Other (OTH)

AF:

0.00

AC:

AN:

2054

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.085

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.62

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.068

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

PhyloP100

1.1

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.39

REVEL

Benign

0.084

Sift

Benign

0.79

Sift4G

Benign

0.087

Polyphen

0.0010

Vest4

0.18

MutPred

0.16

Gain of helix (P = 0.0078);

MVP

0.13

MPC

0.86

ClinPred

0.040

GERP RS

1.2

PromoterAI

0.20

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.064

gMVP

0.29

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over