NM_018340.3:c.586C>G

Variant names:

• chr16-12704753-G-C
• NM_018340.3:c.586C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018340.3(CPPED1):​c.586C>G​(p.His196Asp) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPPED1 NM_018340.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00300
• Publications: 0 publications found

Genes affected

CPPED1 (HGNC:25632): (calcineurin like phosphoesterase domain containing 1) Predicted to enable metal ion binding activity; protein serine phosphatase activity; and protein threonine phosphatase activity. Predicted to be involved in protein dephosphorylation. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05382672).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018340.3. 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
	CPPED1	NM_018340.3	MANE Select	c.586C>G	p.His196Asp	missense	Exon 3 of 4	NP_060810.2	Q9BRF8-1
	CPPED1	NM_001099455.2		c.290-39638C>G		intron	N/A	NP_001092925.1	Q9BRF8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPPED1	ENST00000381774.9	TSL:1 MANE Select	c.586C>G	p.His196Asp	missense	Exon 3 of 4	ENSP00000371193.4	Q9BRF8-1
	CPPED1	ENST00000433677.6	TSL:1	c.290-39638C>G		intron	N/A	ENSP00000411127.2	Q9BRF8-2
	CPPED1	ENST00000898262.1		c.586C>G	p.His196Asp	missense	Exon 3 of 5	ENSP00000568321.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.039
DANN	Benign	0.59
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.18	N
PhyloP100		-0.0030
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.15
Sift	Benign	0.53	T
Sift4G	Benign	0.61	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.28		Gain of relative solvent accessibility (P = 0.0999)
MVP		0.19
MPC		0.068
ClinPred		0.029	T
GERP RS		-1.9
Varity_R		0.034
gMVP		0.25

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

Other links and lift over

hg19: chr16-12798610;