rs775916081

Variant names:

• chr6-30069239-C-G
• NM_021959.3:c.314C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-30069239-C-G
• chr6-30069239-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021959.3(PPP1R11):​c.314C>G​(p.Pro105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P105L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PPP1R11 NM_021959.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469

Genes affected

PPP1R11 (HGNC:9285): (protein phosphatase 1 regulatory inhibitor subunit 11) This gene encodes a specific inhibitor of protein phosphatase-1 (PP1) with a differential sensitivity toward the metal-independent and metal-dependent forms of PP1. The gene is located within the major histocompatibility complex class I region on chromosome 6. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05710432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R11	NM_021959.3	c.314C>G	p.Pro105Arg	missense_variant	Exon 3 of 3	ENST00000376772.8	NP_068778.1
PPP1R11	XM_047419279.1	c.314C>G	p.Pro105Arg	missense_variant	Exon 4 of 4		XP_047275235.1
PPP1R11	XM_047419280.1	c.314C>G	p.Pro105Arg	missense_variant	Exon 5 of 5		XP_047275236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R11	ENST00000376772.8	c.314C>G	p.Pro105Arg	missense_variant	Exon 3 of 3	1	NM_021959.3	ENSP00000365963.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460452 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726552

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Benign	0.0080	T;T;T;T;T;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.021	N
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.057	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	.;L;.;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.030	N;N;N;N;N;N
REVEL	Benign	0.030
Sift	Benign	0.078	T;T;T;T;T;T
Sift4G	Benign	0.086	T;T;T;T;T;T
Polyphen		0.0	.;B;.;.;.;.
Vest4		0.14
MutPred		0.19		.;Loss of glycosylation at P105 (P = 0.0211);.;.;.;.;
MVP		0.043
MPC		1.0
ClinPred		0.064	T
GERP RS		2.3
Varity_R		0.034
gMVP		0.23

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: chr6-30037016;