Genetic Variant NM_032595.5:c.1092G>T (chr17-50149422-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_032595.5(PPP1R9B):c.1092G>T(p.Arg364Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,610,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R364R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PPP1R9B
NM_032595.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.332

Publications

0 publications found

Variant links:

Genes affected

PPP1R9B (HGNC:9298): (protein phosphatase 1 regulatory subunit 9B) This gene encodes a scaffold protein that functions as a regulatory subunit of protein phosphatase 1a. Expression of this gene is particularly high in dendritic spines, suggesting that the encoded protein may play a role in receiving signals from the central nervous system. The encoded protein has putative tumor suppressor function and decreased expression has been observed in tumors. [provided by RefSeq, Feb 2014]

PPP1R9B links:

ENSG00000297935 (HGNC:):

ENSG00000297935 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=0.07546121).

BP6

Variant 17-50149422-C-A is Benign according to our data. Variant chr17-50149422-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3031187.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032595.5. 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
	PPP1R9B	NM_032595.5	MANE Select	c.1092G>T	p.Arg364Ser	missense	Exon 1 of 10	NP_115984.3	Q96SB3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPP1R9B	ENST00000612501.2	TSL:1 MANE Select	c.1092G>T	p.Arg364Ser	missense	Exon 1 of 10	ENSP00000478767.1	Q96SB3
PPP1R9B	ENST00000962427.1		c.1092G>T	p.Arg364Ser	missense	Exon 1 of 10	ENSP00000632486.1
PPP1R9B	ENST00000962426.1		c.1092G>T	p.Arg364Ser	missense	Exon 1 of 9	ENSP00000632485.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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

GnomAD2 exomes

AF:

0.0000168

AC:

AN:

237562

AF XY:

0.0000153

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000569

Gnomad FIN exome

AF:

0.0000473

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458056

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33272

American (AMR)

AF:

0.00

AC:

AN:

44378

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86092

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

52026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110674

Other (OTH)

AF:

0.00

AC:

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

AF:

0.0000263

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

PPP1R9B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0060

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.57

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.075

PhyloP100

0.33

PrimateAI

Uncertain

0.61

Sift4G

Benign

0.48

Vest4

0.15

MVP

0.34

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

gMVP

0.23

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over