5-33944787-A-G
Variant summary
Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1PP3_ModeratePP5
The NM_016180.5(SLC45A2):c.1454T>C(p.Leu485Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 14/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_016180.5 missense
Scores
Clinical Significance
Conservation
Publications
- oculocutaneous albinism type 4Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
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ACMG classification
Our verdict: Uncertain_significance. The variant received 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC45A2 | NM_016180.5 | c.1454T>C | p.Leu485Pro | missense_variant | Exon 7 of 7 | ENST00000296589.9 | NP_057264.4 | |
SLC45A2 | XM_047417259.1 | c.1214T>C | p.Leu405Pro | missense_variant | Exon 7 of 7 | XP_047273215.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152224Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000518 AC: 13AN: 251174 AF XY: 0.0000295 show subpopulations
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727242 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74370 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 25326637) -
This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 485 of the SLC45A2 protein (p.Leu485Pro). This variant is present in population databases (rs749544685, gnomAD 0.03%). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 25326637; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 242519). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SLC45A2 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. -
Oculocutaneous albinism type 4;C2673584:SKIN/HAIR/EYE PIGMENTATION 5, BLACK/NONBLACK HAIR Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at