1-65570508-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002303.6(LEPR):āc.76T>Cā(p.Tyr26His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,822 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 (ā ).
Frequency
Consequence
NM_002303.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEPR | NM_002303.6 | c.76T>C | p.Tyr26His | missense_variant | 4/20 | ENST00000349533.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEPR | ENST00000349533.11 | c.76T>C | p.Tyr26His | missense_variant | 4/20 | 1 | NM_002303.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152274Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250936Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135676
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461548Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727068
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152274Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74392
ClinVar
Submissions by phenotype
LEPR-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 30, 2023 | The LEPR c.76T>C variant is predicted to result in the amino acid substitution p.Tyr26His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0087% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-66036191-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at