chr15-48121062-CCAAACATGGG-C
Position:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_205850.3(SLC24A5):c.20_29del(p.Gln7ArgfsTer61) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SLC24A5
NM_205850.3 frameshift
NM_205850.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.89
Genes affected
SLC24A5 (HGNC:20611): (solute carrier family 24 member 5) This gene is a member of the potassium-dependent sodium/calcium exchanger family and encodes an intracellular membrane protein with 2 large hydrophilic loops and 2 sets of multiple transmembrane-spanning segments. Sequence variation in this gene has been associated with differences in skin pigmentation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 31 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-48121062-CCAAACATGGG-C is Pathogenic according to our data. Variant chr15-48121062-CCAAACATGGG-C is described in ClinVar as [Pathogenic]. Clinvar id is 1408941.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-48121062-CCAAACATGGG-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC24A5 | NM_205850.3 | c.20_29del | p.Gln7ArgfsTer61 | frameshift_variant | 1/9 | ENST00000341459.8 | |
SLC24A5 | XM_047432394.1 | c.20_29del | p.Gln7ArgfsTer61 | frameshift_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC24A5 | ENST00000341459.8 | c.20_29del | p.Gln7ArgfsTer61 | frameshift_variant | 1/9 | 1 | NM_205850.3 | P1 | |
SLC24A5 | ENST00000449382.2 | c.20_29del | p.Gln7ArgfsTer54 | frameshift_variant | 1/8 | 1 | |||
SLC24A5 | ENST00000482911.2 | c.20_29del | p.Gln7ArgfsTer61 | frameshift_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2022 | This sequence change creates a premature translational stop signal (p.Gln7Argfs*61) in the SLC24A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC24A5 are known to be pathogenic (PMID: 23985994, 26686029). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1408941). This premature translational stop signal has been observed in individual(s) with oculocutaneous albinism (PMID: 29345414). This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.