14-23571244-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001146028.2(JPH4):c.1487C>T(p.Pro496Leu) 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 1,610,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001146028.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
JPH4 | NM_001146028.2 | c.1487C>T | p.Pro496Leu | missense_variant | 5/6 | ENST00000356300.9 | NP_001139500.1 | |
JPH4 | NM_032452.3 | c.1487C>T | p.Pro496Leu | missense_variant | 6/7 | NP_115828.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
JPH4 | ENST00000356300.9 | c.1487C>T | p.Pro496Leu | missense_variant | 5/6 | 1 | NM_001146028.2 | ENSP00000348648 | P1 | |
JPH4 | ENST00000397118.7 | c.1487C>T | p.Pro496Leu | missense_variant | 6/7 | 1 | ENSP00000380307 | P1 | ||
JPH4 | ENST00000544177.1 | c.482C>T | p.Pro161Leu | missense_variant | 3/4 | 2 | ENSP00000439562 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000286 AC: 7AN: 245096Hom.: 0 AF XY: 0.0000226 AC XY: 3AN XY: 132670
GnomAD4 exome AF: 0.000171 AC: 250AN: 1458112Hom.: 0 Cov.: 32 AF XY: 0.000164 AC XY: 119AN XY: 725072
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74332
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 31, 2024 | The c.1487C>T (p.P496L) alteration is located in exon 6 (coding exon 4) of the JPH4 gene. This alteration results from a C to T substitution at nucleotide position 1487, causing the proline (P) at amino acid position 496 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at