17-79735641-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_178543.5(ENPP7):c.998A>G(p.Tyr333Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,610,896 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 1 hom. )
Consequence
ENPP7
NM_178543.5 missense
NM_178543.5 missense
Scores
4
10
2
Clinical Significance
Conservation
PhyloP100: 1.65
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.833
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENPP7 | NM_178543.5 | c.998A>G | p.Tyr333Cys | missense_variant | 3/6 | ENST00000328313.10 | |
ENPP7 | XM_011524737.2 | c.1091A>G | p.Tyr364Cys | missense_variant | 3/5 | ||
ENPP7 | XR_001752505.2 | n.1195A>G | non_coding_transcript_exon_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENPP7 | ENST00000328313.10 | c.998A>G | p.Tyr333Cys | missense_variant | 3/6 | 1 | NM_178543.5 | P1 | |
ENPP7 | ENST00000576512.1 | c.101A>G | p.Tyr34Cys | missense_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152094Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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32
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GnomAD3 exomes AF: 0.000101 AC: 25AN: 248454Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 134560
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GnomAD4 exome AF: 0.000165 AC: 240AN: 1458802Hom.: 1 Cov.: 35 AF XY: 0.000157 AC XY: 114AN XY: 725102
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GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74290
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 26, 2021 | The c.998A>G (p.Y333C) alteration is located in exon 3 (coding exon 3) of the ENPP7 gene. This alteration results from a A to G substitution at nucleotide position 998, causing the tyrosine (Y) at amino acid position 333 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.
REVEL
Pathogenic
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at