15-48134957-GTATAA-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_205850.3(SLC24A5):c.568_572del(p.Ile190Ter) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,611,430 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
SLC24A5
NM_205850.3 frameshift
NM_205850.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.41
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 undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-48134957-GTATAA-G is Pathogenic according to our data. Variant chr15-48134957-GTATAA-G is described in ClinVar as [Pathogenic]. Clinvar id is 1929456.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-48134957-GTATAA-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC24A5 | NM_205850.3 | c.568_572del | p.Ile190Ter | frameshift_variant | 5/9 | ENST00000341459.8 | |
MYEF2 | NM_016132.5 | c.*7946_*7950del | 3_prime_UTR_variant | 17/17 | ENST00000324324.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC24A5 | ENST00000341459.8 | c.568_572del | p.Ile190Ter | frameshift_variant | 5/9 | 1 | NM_205850.3 | P1 | |
SLC24A5 | ENST00000449382.2 | c.388_392del | p.Ile130Ter | frameshift_variant | 4/8 | 1 | |||
MYEF2 | ENST00000324324.12 | c.*7946_*7950del | 3_prime_UTR_variant | 17/17 | 1 | NM_016132.5 | P4 | ||
SLC24A5 | ENST00000463289.1 | n.328_332del | non_coding_transcript_exon_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 151998Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250638Hom.: 1 AF XY: 0.0000664 AC XY: 9AN XY: 135468
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1459432Hom.: 0 AF XY: 0.0000179 AC XY: 13AN XY: 725800
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 151998Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74264
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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 | Jun 05, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant is also known as p. IIe189Ilefs*1. This premature translational stop signal has been observed in individual(s) with oculocutaneous albinism (PMID: 32274888). This variant is present in population databases (rs779087076, gnomAD 0.04%). This sequence change creates a premature translational stop signal (p.Ile190*) 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). - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at