6-85450362-G-T
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_002526.4(NT5E):c.223G>T(p.Glu75Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000658 in 1,595,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000071 ( 0 hom. )
Consequence
NT5E
NM_002526.4 stop_gained
NM_002526.4 stop_gained
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 3.64
Genes affected
NT5E (HGNC:8021): (5'-nucleotidase ecto) The protein encoded by this gene is a plasma membrane protein that catalyzes the conversion of extracellular nucleotides to membrane-permeable nucleosides. The encoded protein is used as a determinant of lymphocyte differentiation. Defects in this gene can lead to the calcification of joints and arteries. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NT5E | NM_002526.4 | c.223G>T | p.Glu75Ter | stop_gained | 1/9 | ENST00000257770.8 | |
NT5E | NM_001204813.2 | c.223G>T | p.Glu75Ter | stop_gained | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NT5E | ENST00000257770.8 | c.223G>T | p.Glu75Ter | stop_gained | 1/9 | 1 | NM_002526.4 | P1 | |
NT5E | ENST00000369646.7 | c.223G>T | p.Glu75Ter | stop_gained | 1/3 | 1 | |||
NT5E | ENST00000369651.7 | c.223G>T | p.Glu75Ter | stop_gained | 1/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000472 AC: 10AN: 211716Hom.: 0 AF XY: 0.0000348 AC XY: 4AN XY: 114882
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GnomAD4 exome AF: 0.0000714 AC: 103AN: 1443416Hom.: 0 Cov.: 32 AF XY: 0.0000642 AC XY: 46AN XY: 716186
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74360
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ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
NT5E-related disorder Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpreted as Uncertain significance and reported on 07-23-2021 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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