20-38908098-A-C

Position:

• chr20-38908098-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015568.4(PPP1R16B):​c.1099A>C​(p.Ile367Leu) 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. 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: 4.95

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=0.19680351).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R16B	NM_015568.4	c.1099A>C	p.Ile367Leu	missense_variant	10/11	ENST00000299824.6
PPP1R16B	NM_001172735.3	c.973A>C	p.Ile325Leu	missense_variant	9/10
PPP1R16B	XM_011528768.4	c.1111A>C	p.Ile371Leu	missense_variant	9/10
PPP1R16B	XM_047440086.1	c.502A>C	p.Ile168Leu	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R16B	ENST00000299824.6	c.1099A>C	p.Ile367Leu	missense_variant	10/11	1	NM_015568.4	P1
PPP1R16B	ENST00000373331.2	c.973A>C	p.Ile325Leu	missense_variant	9/10	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Dec 17, 2023

The c.1099A>C (p.I367L) alteration is located in exon 10 (coding exon 9) of the PPP1R16B gene. This alteration results from a A to C substitution at nucleotide position 1099, causing the isoleucine (I) at amino acid position 367 to be replaced by a leucine (L). 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	0.17
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.097	T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.050	N;N
REVEL	Benign	0.14
Sift	Benign	0.12	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.021	B;.
Vest4		0.31
MutPred		0.35		Gain of catalytic residue at I367 (P = 0.0222);.;
MVP		0.60
MPC		0.48
ClinPred		0.50	T
GERP RS		5.8
Varity_R		0.11
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-37536741;