rs756903324
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003982.4(SLC7A7):c.1262C>T(p.Pro421Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,461,854 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P421P) has been classified as Likely benign.
Frequency
Consequence
NM_003982.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC7A7 | NM_003982.4 | c.1262C>T | p.Pro421Leu | missense_variant | 9/10 | ENST00000674313.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC7A7 | ENST00000674313.1 | c.1262C>T | p.Pro421Leu | missense_variant | 9/10 | NM_003982.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251318Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135824
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461854Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 727226
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Lysinuric protein intolerance Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 421 of the SLC7A7 protein (p.Pro421Leu). This variant is present in population databases (rs756903324, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SLC7A7-related conditions. ClinVar contains an entry for this variant (Variation ID: 529503). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at