NM_015568.4:c.715A>G

Variant names:

• chr20-38905987-A-G
• NM_015568.4:c.715A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015568.4(PPP1R16B):​c.715A>G​(p.Asn239Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP1R16B NM_015568.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.63
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015568.4. 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
	PPP1R16B	NM_015568.4	MANE Select	c.715A>G	p.Asn239Asp	missense	Exon 7 of 11	NP_056383.1	Q96T49-1
	PPP1R16B	NM_001172735.3		c.697-992A>G		intron	N/A	NP_001166206.1	Q96T49-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R16B	ENST00000299824.6	TSL:1 MANE Select	c.715A>G	p.Asn239Asp	missense	Exon 7 of 11	ENSP00000299824.1	Q96T49-1
	PPP1R16B	ENST00000969166.1		c.715A>G	p.Asn239Asp	missense	Exon 7 of 11	ENSP00000639225.1
	PPP1R16B	ENST00000969164.1		c.715A>G	p.Asn239Asp	missense	Exon 7 of 11	ENSP00000639223.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.6
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.35
Sift	Benign	0.053	T
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.58		Loss of catalytic residue at N239 (P = 0.0747)
MVP		0.80
MPC		1.4
ClinPred		0.97	D
GERP RS		4.4
Varity_R		0.37
gMVP		0.83
Mutation Taster		=66/34	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

hg19: chr20-37534630;