Genetic Variant ENPP7:p.Pro23Leu (chr17-79731207-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178543.5(ENPP7):c.68C>T(p.Pro23Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000992 in 1,612,106 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ENPP7
NM_178543.5 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.90

Publications

0 publications found

Variant links:

Genes affected

ENPP7 (HGNC:23764): (ectonucleotide pyrophosphatase/phosphodiesterase 7) The protein encoded by this gene is an intestinal alkaline sphingomyelin phosphodiesterase that converts sphingomyelin to ceramide and phosphocholine. The encoded protein is anchored in the cell membrane, and it may function to protect the intestinal mucosa from inflammation and tumorigenesis. This protein is glycosylated and also exhibits lysophosphatidylcholine hydrolase activity. [provided by RefSeq, Oct 2016]

ENPP7 links:

ENSG00000306583 (HGNC:):

ENSG00000306583 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENPP7	NM_178543.5 link	c.68C>T	p.Pro23Leu	missense_variant	Exon 1 of 6	ENST00000328313.10	NP_848638.3	Q6UWV6
ENPP7	XM_011524737.2 link	c.161C>T	p.Pro54Leu	missense_variant	Exon 1 of 5		XP_011523039.2
ENPP7	XR_001752505.2 link	n.265C>T		non_coding_transcript_exon_variant	Exon 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP7	ENST00000328313.10 link	c.68C>T	p.Pro23Leu	missense_variant	Exon 1 of 6	1	NM_178543.5	ENSP00000332656.5		Q6UWV6
ENSG00000306583	ENST00000819500.1 link	n.208+1354G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

249018

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000822

AC:

AN:

1459884

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726258

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33438

American (AMR)

AF:

0.00

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4894

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111878

Other (OTH)

AF:

0.0000332

AC:

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

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:

0.0000263

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000565

Hom.:

Bravo

AF:

0.0000529

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Prostate cancer

Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.97

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.88

PhyloP100

3.9

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.2

REVEL

Uncertain

0.29

Sift

Benign

0.077

Sift4G

Uncertain

0.031

Vest4

0.59

MutPred

0.34

Gain of sheet (P = 0.0028);

MVP

0.68

MPC

0.13

ClinPred

0.31

GERP RS

4.6

PromoterAI

-0.0054

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.70

Mutation Taster

=72/28

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over