NM_015568.4:c.1172C>T

Variant names:

• chr20-38908171-C-T
• rs901625179
• NM_015568.4:c.1172C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015568.4(PPP1R16B):​c.1172C>T​(p.Thr391Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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: 5.70
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1778487).

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.1172C>T	p.Thr391Ile	missense	Exon 10 of 11	NP_056383.1	Q96T49-1
	PPP1R16B	NM_001172735.3		c.1046C>T	p.Thr349Ile	missense	Exon 9 of 10	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.1172C>T	p.Thr391Ile	missense	Exon 10 of 11	ENSP00000299824.1	Q96T49-1
	PPP1R16B	ENST00000969166.1		c.1190C>T	p.Thr397Ile	missense	Exon 10 of 11	ENSP00000639225.1
	PPP1R16B	ENST00000969164.1		c.1172C>T	p.Thr391Ile	missense	Exon 10 of 11	ENSP00000639223.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

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	Benign	0.22
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.7
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.16
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.018	D
Polyphen		0.20	B
Vest4		0.088
MutPred		0.19		Loss of phosphorylation at T391 (P = 0.0169)
MVP		0.37
MPC		0.68
ClinPred		0.77	D
GERP RS		5.8
Varity_R		0.16
gMVP		0.34
Mutation Taster		=68/32	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: rs901625179; hg19: chr20-37536814; COSMIC: COSV55375678;