15-48134886-CT-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_205850.3(SLC24A5):c.493del(p.Ser165GlnfsTer25) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SLC24A5
NM_205850.3 frameshift
NM_205850.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.50
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 15-48134886-CT-C is Pathogenic according to our data. Variant chr15-48134886-CT-C is described in ClinVar as [Pathogenic]. Clinvar id is 817885.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC24A5 | NM_205850.3 | c.493del | p.Ser165GlnfsTer25 | frameshift_variant | 5/9 | ENST00000341459.8 | |
MYEF2 | NM_016132.5 | c.*8021del | 3_prime_UTR_variant | 17/17 | ENST00000324324.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC24A5 | ENST00000341459.8 | c.493del | p.Ser165GlnfsTer25 | frameshift_variant | 5/9 | 1 | NM_205850.3 | P1 | |
SLC24A5 | ENST00000449382.2 | c.313del | p.Ser105GlnfsTer25 | frameshift_variant | 4/8 | 1 | |||
MYEF2 | ENST00000324324.12 | c.*8021del | 3_prime_UTR_variant | 17/17 | 1 | NM_016132.5 | P4 | ||
SLC24A5 | ENST00000463289.1 | n.253del | non_coding_transcript_exon_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
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 | GeneDx | Nov 07, 2018 | The c.493delT variant in the SLC24A5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.493delT variant causes a frameshift starting with codon Serine 165, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 25 of the new reading frame, denoted p.Ser165GlnfsX25. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.493delT variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.493delT as a pathogenic variant. - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at