Genetic Variant NM_018340.3:c.807C>G (chr16-12665024-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_018340.3(CPPED1):c.807C>G(p.Cys269Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,608,968 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CPPED1
NM_018340.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

Publications

0 publications found

Variant links:

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]

CPPED1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

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.807C>G	p.Cys269Trp	missense	Exon 4 of 4	NP_060810.2	Q9BRF8-1
	CPPED1	NM_001099455.2		c.381C>G	p.Cys127Trp	missense	Exon 3 of 3	NP_001092925.1	Q9BRF8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPPED1	ENST00000381774.9	TSL:1 MANE Select	c.807C>G	p.Cys269Trp	missense	Exon 4 of 4	ENSP00000371193.4	Q9BRF8-1
CPPED1	ENST00000433677.6	TSL:1	c.381C>G	p.Cys127Trp	missense	Exon 3 of 3	ENSP00000411127.2	Q9BRF8-2
CPPED1	ENST00000898262.1		c.852C>G	p.Cys284Trp	missense	Exon 5 of 5	ENSP00000568321.1

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000460

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000369

AC:

AN:

243866

AF XY:

0.0000377

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000249

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000961

AC:

AN:

1457082

Hom.:

Cov.:

AF XY:

0.00000965

AC XY:

AN XY:

725050

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32970

American (AMR)

AF:

0.000209

AC:

AN:

42978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39576

South Asian (SAS)

AF:

0.00

AC:

AN:

85800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110432

Other (OTH)

AF:

0.0000166

AC:

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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

AF:

0.0000527

AC:

AN:

151886

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74132

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41346

American (AMR)

AF:

0.000460

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000827

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

PhyloP100

2.2

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-5.4

REVEL

Benign

0.28

Sift

Benign

0.073

Sift4G

Benign

0.082

Polyphen

0.064

Vest4

0.87

MutPred

0.54

Gain of helix (P = 0.0117)

MVP

0.36

MPC

0.084

ClinPred

0.74

GERP RS

4.6

Varity_R

0.49

gMVP

0.58

Mutation Taster

=37/63

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over