rs146764513

Variant names:

• chr19-55092299-C-G
• rs146764513
• NM_017607.4:c.2083G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-55092299-C-G
• chr19-55092299-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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]

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=0.1526342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R12C	NM_017607.4	c.2083G>C	p.Glu695Gln	missense_variant	Exon 19 of 22	ENST00000263433.8	NP_060077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R12C	ENST00000263433.8	c.2083G>C	p.Glu695Gln	missense_variant	Exon 19 of 22	1	NM_017607.4	ENSP00000263433.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000444 AC: 1 AN: 225138 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 122524

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 SAS 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: 2 AN: 1448394 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 719406

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000231

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	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.091
Sift	Benign	0.28	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.99	D;.
Vest4		0.12
MutPred		0.16		Gain of MoRF binding (P = 0.0331);.;
MVP		0.27
MPC		1.1
ClinPred		0.71	D
GERP RS		3.1
Varity_R		0.26
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

LitVar

Other links and lift over

dbSNP: rs146764513; hg19: chr19-55603667;