chr6-85471336-C-A
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_002526.4(NT5E):c.662C>A(p.Ser221Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000391 in 1,612,910 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 Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
NT5E
NM_002526.4 stop_gained
NM_002526.4 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 7.09
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 11 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;
PP5
?
Variant 6-85471336-C-A is Pathogenic according to our data. Variant chr6-85471336-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 29687.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NT5E | NM_002526.4 | c.662C>A | p.Ser221Ter | stop_gained | 3/9 | ENST00000257770.8 | |
NT5E | NM_001204813.2 | c.662C>A | p.Ser221Ter | stop_gained | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NT5E | ENST00000257770.8 | c.662C>A | p.Ser221Ter | stop_gained | 3/9 | 1 | NM_002526.4 | P1 | |
NT5E | ENST00000369646.7 | c.662C>A | p.Ser221Ter | stop_gained | 3/3 | 1 | |||
NT5E | ENST00000369651.7 | c.662C>A | p.Ser221Ter | stop_gained | 3/8 | 2 | |||
NT5E | ENST00000416334.5 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152016Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251184Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135746
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GnomAD4 exome AF: 0.0000287 AC: 42AN: 1460894Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 726750
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GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152016Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74244
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hereditary arterial and articular multiple calcification syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 03, 2011 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;D
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