19-55231482-T-C

Position:

• chr19-55231482-T-C

Variant summary

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

The NM_014931.4(PPP6R1):​c.2387A>G​(p.Gln796Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP6R1 NM_014931.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.484

Genes affected

PPP6R1 (HGNC:29195): (protein phosphatase 6 regulatory subunit 1) Protein phosphatase regulatory subunits, such as SAPS1, modulate the activity of protein phosphatase catalytic subunits by restricting substrate specificity, recruiting substrates, and determining the intracellular localization of the holoenzyme. SAPS1 is a regulatory subunit for the protein phosphatase-6 catalytic subunit (PPP6C; MIM 612725) (Stefansson and Brautigan, 2006 [PubMed 16769727]).[supplied by OMIM, Nov 2010]

PPP6R1 (HGNC:):

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=0.14688903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP6R1	NM_014931.4	c.2387A>G	p.Gln796Arg	missense_variant	21/24	ENST00000412770.7	NP_055746.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP6R1	ENST00000412770.7	c.2387A>G	p.Gln796Arg	missense_variant	21/24	1	NM_014931.4	ENSP00000414202.1
PPP6R1	ENST00000587283.5	c.2387A>G	p.Gln796Arg	missense_variant	20/23	1		ENSP00000467521.1
PPP6R1	ENST00000587457.1	n.1382A>G		non_coding_transcript_exon_variant	4/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Nov 10, 2024

The c.2387A>G (p.Q796R) alteration is located in exon 21 (coding exon 20) of the PPP6R1 gene. This alteration results from a A to G substitution at nucleotide position 2387, causing the glutamine (Q) at amino acid position 796 to be replaced by an arginine (R). 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	0.069
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.043
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.66	.;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.49	N;.
REVEL	Benign	0.061
Sift	Benign	0.17	T;.
Sift4G	Benign	0.46	T;T
Polyphen		0.42	B;B
Vest4		0.46
MutPred		0.34		Gain of MoRF binding (P = 0.0676);Gain of MoRF binding (P = 0.0676);
MVP		0.16
MPC		0.18
ClinPred		0.40	T
GERP RS		3.8
Varity_R		0.046
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-55742850;