Genetic Variant ENPP7:p.Thr155Lys (chr17-79735107-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_178543.5(ENPP7):c.464C>A(p.Thr155Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. T155M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ENPP7
NM_178543.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2670167).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178543.5. 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
	ENPP7	NM_178543.5	MANE Select	c.464C>A	p.Thr155Lys	missense	Exon 3 of 6	NP_848638.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENPP7	ENST00000328313.10	TSL:1 MANE Select	c.464C>A	p.Thr155Lys	missense	Exon 3 of 6	ENSP00000332656.5	Q6UWV6
ENPP7	ENST00000864480.1		c.464C>A	p.Thr155Lys	missense	Exon 4 of 7	ENSP00000534539.1
ENPP7	ENST00000864481.1		c.464C>A	p.Thr155Lys	missense	Exon 3 of 5	ENSP00000534540.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726664

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111994

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

0.23

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.92

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.077

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.80

PhyloP100

1.3

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.8

REVEL

Benign

0.23

Sift

Benign

0.23

Sift4G

Benign

0.34

Vest4

0.34

MutPred

0.62

Gain of methylation at T155 (P = 0.0049)

MVP

0.61

MPC

0.21

ClinPred

0.30

GERP RS

4.0

PromoterAI

-0.13

Neutral

(source)

gMVP

0.81

Mutation Taster

=81/19

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over