rs752594411
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS1
The NM_002230.4(JUP):āc.1862T>Cā(p.Ile621Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000645 in 1,613,348 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. I621I) has been classified as Likely benign.
Frequency
Consequence
NM_002230.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JUP | NM_002230.4 | c.1862T>C | p.Ile621Thr | missense_variant | 11/14 | ENST00000393931.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JUP | ENST00000393931.8 | c.1862T>C | p.Ile621Thr | missense_variant | 11/14 | 1 | NM_002230.4 | P1 | |
JUP | ENST00000310706.9 | c.1862T>C | p.Ile621Thr | missense_variant | 11/15 | 1 | P1 | ||
JUP | ENST00000393930.5 | c.1862T>C | p.Ile621Thr | missense_variant | 11/15 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000855 AC: 13AN: 152062Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000160 AC: 40AN: 249274Hom.: 0 AF XY: 0.000141 AC XY: 19AN XY: 135022
GnomAD4 exome AF: 0.0000623 AC: 91AN: 1461168Hom.: 0 Cov.: 38 AF XY: 0.0000605 AC XY: 44AN XY: 726798
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74410
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 18, 2017 | The I621T variant of uncertain significance in the JUP gene has not been published as pathogenic or been reported as benign to our knowledge. The I621T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, to our knowledge no studies have been performed to determine the functional effect of the I621T variant. Furthermore, the I621T variant was observed in 8/8,426 alleles from individuals of East Asian ancestry, 5/5,786 alleles from individuals of European (Finnish) ancestry, and 6/64,012 alleles from individuals of European (Non-Finnish) ancestry in the Exome Aggregation Consortium (ExAC) dataset (Lek et al., 2016). - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2019 | - - |
Naxos disease;C1969081:Arrhythmogenic right ventricular dysplasia 12 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 01, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 09, 2022 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at