dbSNP rs146764513: PPP1R12C:p.Glu695Gln (chr19-55092299-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017607.4(PPP1R12C):c.2083G>C(p.Glu695Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. E695D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PPP1R12C
NM_017607.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.139

Publications

4 publications found

Variant links:

Genes affected

PPP1R12C (HGNC:14947): (protein phosphatase 1 regulatory subunit 12C) The gene encodes a subunit of myosin phosphatase. The encoded protein regulates the catalytic activity of protein phosphatase 1 delta and assembly of the actin cytoskeleton. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

PPP1R12C links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1526342).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017607.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R12C	NM_017607.4	MANE Select	c.2083G>C	p.Glu695Gln	missense	Exon 19 of 22	NP_060077.1	Q9BZL4-1
	PPP1R12C	NM_001271618.2		c.2077G>C	p.Glu693Gln	missense	Exon 19 of 22	NP_001258547.1	Q9BZL4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPP1R12C	ENST00000263433.8	TSL:1 MANE Select	c.2083G>C	p.Glu695Gln	missense	Exon 19 of 22	ENSP00000263433.1	Q9BZL4-1
PPP1R12C	ENST00000592993.1	TSL:1	c.1945G>C	p.Glu649Gln	missense	Exon 19 of 22	ENSP00000465957.1	K7EL81
PPP1R12C	ENST00000854894.1		c.2080G>C	p.Glu694Gln	missense	Exon 19 of 22	ENSP00000524953.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000444

AC:

AN:

225138

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000308

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1448394

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33218

American (AMR)

AF:

0.0000231

AC:

AN:

43302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25782

East Asian (EAS)

AF:

0.00

AC:

AN:

39182

South Asian (SAS)

AF:

0.00

AC:

AN:

84098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1105852

Other (OTH)

AF:

0.00

AC:

AN:

59848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.70

M_CAP

Benign

0.059

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

0.14

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.2

REVEL

Benign

0.091

Sift

Benign

0.28

Sift4G

Benign

0.45

Polyphen

0.99

Vest4

0.12

MutPred

0.16

Gain of MoRF binding (P = 0.0331)

MVP

0.27

MPC

1.1

ClinPred

0.71

GERP RS

3.1

Varity_R

0.26

gMVP

0.23

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over