17-50149422-C-G

Variant names:

• chr17-50149422-C-G
• rs367543189
• NM_032595.5:c.1092G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032595.5(PPP1R9B):​c.1092G>C​(p.Arg364Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,458,058 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. R364R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: PPP1R9B NM_032595.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• Publications: 0 publications found

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]

ENSG00000297935 (HGNC:):

ACMG classification

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=0.06785473).

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>C	p.Arg364Ser	missense	Exon 1 of 10	NP_115984.3	Q96SB3

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000379 AC: 9 AN: 237562 AF XY: 0.0000459

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000883

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000569

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000952

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1458058 Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9 AN XY: 725342

African (AFR) AF: 0.00 AC: 0 AN: 33272

American (AMR) AF: 0.0000676 AC: 3 AN: 44378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39646

South Asian (SAS) AF: 0.0000813 AC: 7 AN: 86092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110674

Other (OTH) AF: 0.0000166 AC: 1 AN: 60168

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000167 AC: 2

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.0060	T
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.068	T
PhyloP100		0.33
PrimateAI	Uncertain	0.61	T
Sift4G	Benign	0.48	T
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

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

Other links and lift over

dbSNP: rs367543189; hg19: chr17-48226787; COSMIC: COSV57542097; COSMIC: COSV57542097;