chr20-38908171-C-T

Position:

• chr20-38908171-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R16B	NM_015568.4	c.1172C>T	p.Thr391Ile	missense_variant	10/11	ENST00000299824.6	NP_056383.1
PPP1R16B	NM_001172735.3	c.1046C>T	p.Thr349Ile	missense_variant	9/10		NP_001166206.1
PPP1R16B	XM_011528768.4	c.1184C>T	p.Thr395Ile	missense_variant	9/10		XP_011527070.1
PPP1R16B	XM_047440086.1	c.575C>T	p.Thr192Ile	missense_variant	6/7		XP_047296042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R16B	ENST00000299824.6	c.1172C>T	p.Thr391Ile	missense_variant	10/11	1	NM_015568.4	ENSP00000299824	P1
PPP1R16B	ENST00000373331.2	c.1046C>T	p.Thr349Ile	missense_variant	9/10	5		ENSP00000362428

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.1172C>T (p.T391I) alteration is located in exon 10 (coding exon 9) of the PPP1R16B gene. This alteration results from a C to T substitution at nucleotide position 1172, causing the threonine (T) at amino acid position 391 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.018	D;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

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

LitVar

Other links and lift over

dbSNP: rs901625179; hg19: chr20-37536814; COSMIC: COSV55375678;