NM_015568.4:c.475G>C

Variant names:

• chr20-38900588-G-C
• NM_015568.4:c.475G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015568.4(PPP1R16B):​c.475G>C​(p.Asp159His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PPP1R16B NM_015568.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.15

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R16B	NM_015568.4	c.475G>C	p.Asp159His	missense_variant	Exon 5 of 11	ENST00000299824.6	NP_056383.1
PPP1R16B	NM_001172735.3	c.475G>C	p.Asp159His	missense_variant	Exon 5 of 10		NP_001166206.1
PPP1R16B	XM_011528768.4	c.487G>C	p.Asp163His	missense_variant	Exon 4 of 10		XP_011527070.1
PPP1R16B	XM_047440086.1	c.-26-2080G>C		intron_variant	Intron 1 of 6		XP_047296042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R16B	ENST00000299824.6	c.475G>C	p.Asp159His	missense_variant	Exon 5 of 11	1	NM_015568.4	ENSP00000299824.1
PPP1R16B	ENST00000373331.2	c.475G>C	p.Asp159His	missense_variant	Exon 5 of 10	5		ENSP00000362428.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449686 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 720648

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.8	D;D
REVEL	Uncertain	0.53
Sift	Benign	0.063	T;D
Sift4G	Benign	0.063	T;T
Polyphen		1.0	D;.
Vest4		0.92
MutPred		0.58		Gain of catalytic residue at L161 (P = 0.0763);Gain of catalytic residue at L161 (P = 0.0763);
MVP		0.80
MPC		2.6
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.41
gMVP		0.81

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: chr20-37529231;